melanoma committee agenda 2002/melanoma.pdfmelanoma. publication status. dr. whitehead s9622...

APRIL 19 - 21, 2002 SOUTHWEST ONCOLOGY GROUP MELANOMA 1

MELANOMA COMMITTEE

Chair: Vernon K. Sondak, M.D. Vice Chair: Lawrence E. Flaherty, M.D.

Statisticians: P Y Liu, Ph.D.

James Moon, M.S.

Data Coordinators: Camille White, B.S., C.C.R.P. Larry Kaye, B.A.

Protocol Coordinator: Connie Ballon-Almanza, B.S.

Medical Oncology: Lawrence E. Flaherty, M.D. Pathology: Ralph J. Tuthill, M.D.

Radiation Oncology: James G. Douglas, M.D. Surgery: James A. Warneke, M.D.

Melanoma Biology: Jeffrey A. Sosman, M.D. Non-Melanoma Skin Cancer: Raymond A. Kempf, M.D., M.Ph.

Cancer Control Liaison: Marie-France Demierre, M.D. Cytogenetics Liaison: Diane L. Persons, M.D

Nurses: Karen L. Mack, R.N.P. Susan Stockton, R.N., B.S.N.

Clinical Research Associates: Renee Robinson, C.C.R.A. Karen G. Egan, B.A., C.C.R.A.

2 MELANOMA SOUTHWEST ONCOLOGY GROUP APRIL 19 - 21, 2002

CONTENTS

Melanoma Committee Agenda ....................................................................................3

Initial Registrations to Therapeutic Studies .................................................................5

Patient Registration by Study and Arm .......................................................................6

E2697 Biologic Intergroup ..........................................................................................7

E3695 Phase III Intergroup..........................................................................................8

E4697 Phase III Intergroup........................................................................................10

S9430 Phase II Intergroup .........................................................................................12

S9431 Biologic ..........................................................................................................14

S0008 Phase III Intergroup ........................................................................................16

S0026 Phase II ...........................................................................................................20

S0116 Phase II ...........................................................................................................21


Melanoma Committee Agenda

Scientific Session

Adjuvant Therapy Trials in Resected Melanoma: When Is a No Treatment Arm Acceptable?

Dr. Urba

Active Studies

S9430 Phase II Trial of Complete Surgical Resection for Stage IV Melanoma with Distant Metastases-Surgical Resection with Biological and Clinical Follow-up.

Dr. Sosman

S9431 Molecular, Cytogenetic, and Cellular Biology Studies in Metastatic Melanoma Patients.

Drs. Sosman, Tuthill and Persons

S0008 Phase III Trial of High Dose Interferon Alfa-2b versus Cisplatin, Vinblastine, DTIC plus IL-2 and Interferon in Patients with High Risk Melanoma.

Dr. Flaherty

S0026 Evaluation of Interferon Alfa-2b and Thalidomide in Patients with Disseminated Malignant Melanoma, Phase II.

Dr. Hutchins

E3695 A Randomized Phase III Trial of Concurrent Biochemotherapy with Cisplatin, Vinblastine, Dacarbazine, IL-2 and Interferon Alfa-2b versus Cisplatin, Vinblastine, Dacarbazine Alone in Patients with Metastatic Malignant Melanoma.

Dr. Flaherty

E2697 Correlation of DNA Damage Index and Clinical Response in the Context of ECOG Trial E3695.

Dr. Sosman

Closed Studies

S9035 Adjuvant Allogeneic Melanoma Vaccine Trial in T3N0M0 Melanoma, Phase III. Update and Publication Status.

Drs. Sondak and Sosman

S9505 Evaluation of Pyrazine Diazohydroxide in Disseminated Malignant Melanoma. Publication Status.

Dr. Whitehead

S9622 Evaluation of CI-980 in Patients with Disseminated Malignant Melanoma and No Prior Chemotherapy. Publication Status.

Dr. Whitehead

S9804 Phase II Trial of Navelbine in Disseminated Malignant Melanoma. Update.

Dr. Whitehead


Proposed Studies

S0116 Phase II Trial of D1/3-MAGE3-His Fusion Protein with Adjuvant SB-AS02B for Patients with Stage IV, M1a or M1b Metastatic Melanoma.

Dr. Weber

S0201 Intergroup Phase III Adjuvant Trial for Intermediate Risk Melanoma.

Dr. Sondak

E1697 Phase III Randomized Study of Four Weeks High Dose IFN-α2b in Stage T3-T4 or N1 (microscopic) Melanoma.

Dr. Flaherty

E4697 Randomized, Placebo-Controlled Phase III Trial of GM-CSF versus Peptide Vaccine versus GM-CSF + Peptide Vaccine versus Placebo.

Dr. Margolin

Gleevec in Merkel Cell Carcinoma Dr. Redman

Other Phase II Agents. Dr. Flaherty

Subcommittee Reports

Pathology Dr. Tuthill

Melanoma Biology Dr. Sosman

Non-Melanoma Skin Cancer Dr. Kempf

Working Group Dr. Sondak


Initial Registrations to Therapeutic Studies

by 12 month Intervals MELANOMA COMMITTEE

0

20

40

60

80

100

120

140

160

180

Time of registration

JAN 1997DEC 1997

57

45

46

JAN 1998DEC 1998

79

44

40

JAN 1999DEC 1999

59

49

52

JAN 2000DEC 2000

42

14

17

JAN 2001DEC 2001

44

9

19

21

MEMBER AFFILIATES CCOP NON-SWOG


Patient Registration by Study and Arm

MELANOMA COMMITTEE

July-Dec

2001 Jan-June 2001 July-Dec

2000 All Patients

E3695 Melan, Adv, CVD +/- IFN/IL-2 * CVD 11 9 12 81 CVD + IFN/IL-2 9 8 11 81 20 17 23 162 E2697 Melan, Biol Ancillary to E3695 * DNA Damage Index 5 5 4 17 S9430 Melan,Adv,Comp Surg Res,Ph II Surgical resection 2 5 2 53 S9431 Melan, Tissues and Serum Tissues and serum 3 5 2 56 S0008 Melan,Adj,HD IFN v CVD+IFN/IL2 Randomization

HD IFN Alfa-2b 12 9 1 22 CVD + IFN/IL-2 19 9 0 28 31 18 1 50

* For non-SWOG coordinated studies only SWOG registrations are shown.


E2697/BIOLOGIC

E2697 Biologic Intergroup Coordinating Group: ECOG

Correlation of DNA Damage Index and Clinical Response in the Context of ECOG Trial E3695

Intergroup Participants: ECOG, SWOG

Study Coordinators: M Atkins (ECOG), J Sosman

Statisticians: P Y Liu, J Moon

Data Coordinators: C White, L Kaye

Date Activated: 2/1/2000

Objectives To determine the extent of cisplatin-induced DNA damage in vitro in PBMC obtained from melanoma patients prior to treatment with chemotherapy or biochemotherapy and correlate the extent of DNA damage with clinical response.

To determine the optimum cisplatin concentration with which to treat PBMC in vitro that will provide the highest positive and negative predictive value for response to both chemotherapy and biochemotherapy.

Patient Population Patients must have been randomized to the parent protocol E3695.

Accrual Goals The accrual goal is 200 patients (100 from the chemotherapy group and 100 from the biochemotherapy group of E3695).

Summary Statement As of December 31, 2001, 72 patients have been registered to this study (17 from the Southwest Oncology Group). All patients enrolled on E3695 need only submit blood samples to be eligible. See E2697 protocol for blood sample submission instructions.

The complete December 2001 summary of this study from ECOG is available on the Southwest Oncology Group web site.

Registration by Institution Registrations ending December 31, 2001

Institutions Total Reg Institutions

Total Reg

Harrington/TexasTech/San Antonio, U of TX 2 Kansas, U of 1Loyola University 2 Mississippi, U of 1San Antonio, U of TX 2 Montana CCOP 1Southeast CCC CCOP 2 Oregon Hlth Sci Univ 1St Louis CCOP 2 Upstate Carolina 1Wichita CCOP 2 Total (11 Institutions) 17


E3695/III

E3695 Phase III Intergroup Coordinating Group: ECOG

A Randomized Phase III Trial of Concurrent Biochemotherapy with Cisplatin, Vinblastine, Dacarbazine, IL-2 and Interferon Alfa-2b versus Cisplatin, Vinblastine, Dacarbazine Alone in Patients with Metastatic

Malignant Melanoma


Study Coordinators: M Atkins (ECOG), L Flaherty, V Sondak




Schema

RANDOMIZE

DTIC/CDDP/Vinblastine (CVD)

DTIC/CDDP/Vinblastine/IL-2/IFN Alpha-2b and G-CSF

Objectives To determine whether an inpatient biochemotherapy of CVD + IL-2/interferon alfa-2b/G-CSF is superior to CVD alone based on survival in patients with metastatic malignant melanoma.

To determine whether this inpatient biochemotherapy is superior to CVD alone based on response rate, response duration, time to treatment failure, percent CR and percent durable CR.

To determine the feasibility of administering this inpatient biochemotherapy regimen to patients with metastatic malignant melanoma in an intergroup multicenter setting.

To determine the toxicity of this inpatient biochemotherapy regimen relative to CVD alone.

Patient Population Patients must have histologically confirmed, surgically incurable metastatic malignant melanoma. Patients must not have active brain metastases or leptomeningeal disease. Patients with history of brain metastases must be three months from definitive therapy and have no evidence of active disease or edema on brain MRI. Patients must have measurable disease.

Patients must not have received any prior systemic therapy for metastatic disease. Patients must not have had prior radiotherapy to areas of measurable disease unless they have clearly progressive disease in this site or there is measurable disease outside the area of prior radiation.

Patients must have ECOG performance status of 0 or 1 and adequate hematologic, renal, cardiac, pulmonary, and hepatic functions. Patients must


E3695/III

be age 18 years or older. Patients with organ allografts or seizure disorders, patients requiring corticosteroids, and patients known to be positive for HIV antibody are ineligible.

Stratification/Descriptive Factors Patients will be stratified by (1) performance status: 0 vs 1; (2) prior interferon: yes vs no; and (3) number of involved sites: 1 vs 2 or 3 vs 4 or more.

Accrual Goals Four hundred sixty-eight eligible patients will be accrued to this study over a 40-month period.

Interim analyses will be performed approximately 12, 19, and 26 months after the trial opens.

Summary Statement As of December 31, 2001, 396 patients have been registered to this study (162 from the Southwest Oncology Group). In an April 1, 2001 amendment, ECOG increased the accrual goal from 264 eligible patients to 468 eligible patients.




Total Reg

Michigan, U of 16 Greater Phoenix CCOP 3Wayne State Univ 16 Loyola University 3San Antonio, U of TX 9 Southeast CCC CCOP 3City of Hope Med Ctr 8 Boston Univ Med Ctr 2Utah, U of 8 Kansas, U of 2Arizona, U of 6 Montana CCOP 2Grand Rapids CCOP 5 New Mexico, U of 2Harrington/TexasTech/San Antonio, U of TX 5 Oregon Hlth Sci Univ 2LSU-Shreveport 5 Ozarks Reg CCOP 2Wichita CCOP 5 Puget Sound 2Atlanta Reg CCOP 4 S Georgia Med Ctr/BAMC/WHMC 2BAMC/WHMC 4 St Mary's Hospital/Colorado, U of 2Columbia River CCOP 4 Tulane University 2Columbia University 4 Upstate Carolina 2St Louis CCOP 4 All Other Institutions 21U of Tennessee MC/San Antonio, U of TX 4 Total (52 Institutions) 162Cleveland Clinic OH 3


E4697/III

E4697 Phase III Intergroup Coordinating Group: ECOG

A Randomized, Placebo-Controlled Phase III Trial of Yeast Derived GM-CSF Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients with "No Evidence of Disease" after Complete

Surgical Resection of "Locally Advanced" and/or Stage IV Melanoma


Study Coordinators: D Lawson (ECOG), K Margolin



Schema

RANDOMIZATI

ON

GM-CSF + peptide vaccine

GM-CSF placebo + peptide vaccine

GM-CSF + peptide placebo

GM-CSF placebo + peptide placebo

HLA-A2+

RANDOMIZATI

ON

HLA-A2-

GM-CSF

GM-CSF placebo

Objectives To compare overall survival, two year survival, and time to progression of patients with completely resected Stage IV melanoma or Stage III melanoma with gross extranodal extension, satellites, and/or intransit lesions, or with other

high risk factors when treated with GM-CSF versus no GM-CSF.

To compare overall survival, two year survival, and time to progression of HLA-A2 positive


E4697/III

patients treated with peptide vaccination versus no peptide vaccination.

To perform descriptive evaluations of overall survival and time to progression of HLA-A2 positive patients treated with GM-CSF plus peptide vaccination versus peptide vaccination alone, GM-CSF plus peptide vaccination versus GM-CSF alone, and GM-CSF plus peptide vaccination versus placebo. In addition, for descriptive purposes, survival and time to progression of HLA-A2 positive patients not receiving peptide vaccination will be compared to that of HLA-A2 negative patients.

To investigate the influence of GM-CSF on circulating dendritic cell numbers in peripheral blood of patients receiving and not receiving GM-CSF.

To investigate, in HLA-A2 positive patients, whether immunization with peptides with or without GM-CSF elicits a measurable T-cell response as assessed by ELISPOT and the MHC tetramer assay, and to investigate the functionality of these cells by intracellular cytokine staining.

Patient Population Patients must have completely resected disease with one of the following: any locoregional recurrence after prior adjuvant interferon or failure on S0008, any local recurrence of disease after adequate surgical excision of the original primary, mucosal melanoma, or Stage IV melanoma of cutaneous, ocular, mucosal, or unknown primary. Provided they are ineligible for S0008 or are considered medically unfit to receive standard high-dose interferon, patients with any clinically evident satellite or intransit disease, Stage III disease with gross extracapsular extension, recurrence in a previously resected nodal basin, four or more involved lymph nodes (or matted lymph nodes), or an ulcerated primary with lymph node involvement are eligible for this study. Patients must have been surgically

rendered free of disease with negative margins on resected specimens. Patients rendered free of disease by non-surgical means are not eligible.

Patients must not have received any adjuvant therapy, (chemotherapy, biologic, or limb perfusion), after the resection(s) that makes them eligible for this trial. One systemic treatment after prior surgery is allowed. Previous radiation therapy, including after the resection, is allowed. Patients must not have had any prior treatment with GM-CSF or any peptides used in this protocol.

Patients HLA-A2 status must be known. Patients must have an ECOG performance status of 0-1, and must be able to self-administer or arrange for administration of subcutaneous injections. Patients must have adequate hematologic and hepatic function. Patients must not have an active infection requiring treatment with parenteral antibiotics. Patients must not have autoimmune disorders, conditions of immunosuppresion or treatment with steroids. Replacement doses of steroids for patients with adrenal insufficiency are allowed.

Stratification/Descriptive Factors Patients are stratified by (1) HLA-A2 status: positive vs negative; (2) site of metastases: visceral vs non-visceral vs both; and (3) number of metastatic lesions: 1 vs 2-3 vs 4 or more.

Accrual Goals The accrual goal is 540 eligible patients, with 90 eligible patients per treatment arm.

Summary Statement ECOG activated this study on December 29, 1999. As of December 31, 2001, 119 patients have been registered. This study has not yet opened in the Southwest Oncology Group.



S9430/II

S9430 Phase II Intergroup Coordinating Group: SWOG

A Phase II Trial of Complete Surgical Resection for Stage IV Melanoma: Surgical Resection with Biological Evaluation and Clinical Follow-Up

Intergroup Participants: SWOG, ECOG

Study Coordinators: J Sosman, V Sondak, R Tuthill, J Kirkwood (ECOG)

Statisticians: J Moon, P Y Liu

Data Coordinators: C White


Objectives To assess the overall survival and progression-free survival of patients with metastatic melanoma (beyond the draining lymph nodes) following complete surgical resection of all known disease.

To determine the ability of the Southwest Oncology Group Melanoma Committee to enroll patients with metastatic melanoma who can be resected to a "disease-free" state, in order to assess the feasibility of future trials of specific interventions in this patient population.

Patient Population Patients must have histologically confirmed Stage IV melanoma that is deemed to be surgically resectable. Patients with multiple resected sites or metastatic melanoma from an unknown primary site are eligible as long as all known disease will be grossly resected. Patients with recurrence in iliac lymph nodes following inguinal lymph node dissection are eligible.

Prior non-protocol surgery is allowed, but must have been completed at least 14 days prior to registration. Prior radiation therapy, chemotherapy, or immunotherapy are allowed, but must have been completed at least 28 days prior to registration. Patients must have a SWOG performance status of 0-2. Simultaneous registration to S9431 is required.

Patients must be registered prior to protocol surgery.

Stratification/Descriptive Factors Patients will be described by (1) prior surgery: yes vs no; (2) prior systemic therapy: yes vs no; (3) performance status: 0-1 vs 2; (4) metastatic disease status: visceral vs non-visceral; (5) primary site: known vs unknown; and (6) prior adjuvant interferon: yes vs no.

Accrual Goals The accrual goal is 100 eligible patients with gross disease completely resected.

Summary Statement As of December 2001, 53 patients were registered to this study. One patient is currently listed as ineligible due to insufficient baseline documentation. ECOG joined the study on March 24, 2000. In a July 15, 2000 revision, the accrual goal was increased from 50 to 100 eligible patients with gross disease completely resected.

Five eligible patients are not analyzable: three who did not have disease completely resected, one whose specimen was free of tumor, and one who did not undergo surgical resection (a major protocol deviation).

Out of 41 analyzable patients evaluated, two experienced surgical toxicities: one patient with Grade 1 hemorrhage and Grade 1 wound infection, the other with Grade 1 wound infection. A third patient experienced ARDS, (along with thrombocytopenia, hyponatremia, and thrombosis/embolism), 34 days following protocol surgery. This is tentatively coded as a Grade 4 toxicity while the relationship to protocol surgery is still under review.


S9430/II



Total Reg

Michigan, U of 16 Carilion Medical Ctr/Temple University 1Oregon Hlth Sci Univ 15 Kansas City CCOP 1Wayne State Univ 5 Montana CCOP 1City of Hope Med Ctr 4 New Mexico, U of 1Salem Hospital/Oregon Hlth Sci Univ 2 Puget Sound 1Utah, U of 2 South Alabama CCOP 1Wichita CCOP 2 Total (14 Institutions) 53Arizona, U of 1

Registration, Eligibility, and Evaluability Registrations ending December 31, 2001; Data as of January 29, 2002

Surgical resection

Surgical resection

NUMBER REGISTERED 53 TOXICITY ASSESSMENT 47 INELIGIBLE 1 Evaluable 41 Insufficient Documentation 1 Too Early 6 Reversible 1 ELIGIBLE 52 Not Analyzable 5

Patient Characteristics Registrations ending December 31, 2001; Data as of January 29, 2002

Surgical resection

(n=47) Surgical resection

(n=47)

AGE PERFORMANCE STATUS Median 53 .0 0 or 1 47 100% Minimum 18 2 0 0% Maximum 79 METASTATIC DISEASE SEX Non-visceral 33 70% Males 33 70% Visceral 14 30% Females 14 30% PRIMARY SITE RACE Known 46 98% White (Non-Hispanic) 45 96% Unknown 1 2% Black (Non-Hispanic) 1 2% American Indian 1 2% PRIOR ADJUVANT INTERFERON Yes 22 47%PRIOR SURGERY No 25 53% Yes 45 96% No 2 4% PRIOR SYSTEMIC TREATMENT Yes 23 49% No 24 51%


S9431/BIOLOGIC

S9431 Biologic Coordinating Group: SWOG

Cytogenetic, Molecular and Cellular Biology Studies in Metastatic Melanoma Patients, Ancillary

Intergroup Participants: SWOG, ECOG

Study Coordinators: J Sosman, V Sondak, R Tuthill, C Fenoglio-Preiser, M Slovak, J Kirkwood (ECOG)




Objectives To characterize the frequency of non-random cytogenetic abnormalities in regional and distant melanoma metastases and explore their association with clinical outcome of melanoma patients enrolled onto Southwest Oncology Group trials.

To characterize the frequency of specific genetic alterations at either the DNA, mRNA, or protein level and explore the association of these abnormalities with clinical outcome in patients with regional and distant metastases who are enrolled on Southwest Oncology Group melanoma trials.

To characterize the host immunologic response to metastatic melanoma by determining whether the in-vivo pattern of cytokine expression is consistent with specific subsets of T helper cells (TH1 or TH2) within melanoma deposits.

To explore whether host immunologic response varies based on the site of metastatic disease and/or correlates with clinical outcome in patients enrolled on Southwest Oncology Group trials.

To obtain paraffin embedded tumor blocks, peripheral blood, and sera from patients with metastatic melanoma to form a tissue, cell and serum bank for future studies.

Patient Population To be eligible for S9431, the patient must have been registered, or is planned to be registered

within 56 days, to a Southwest Oncology Group melanoma treatment protocol. Patients for whom the only registration is to a non-SWOG coordinated study are not eligible.

Summary Statement As of December 31, 2001, 56 patients were registered to this study. One patient with no registration to a SWOG-coordinated treatment trial was ineligible. One patient, after registering to S9431, refused randomization to S0008, thus is not analyzable. Among the remaining eligible patients, 53 were from treatment trial S9430 and one was from treatment trial S9350. ECOG joined the study on March 24, 2000.

Investigators are strongly encouraged to submit snap-frozen tissue samples in order to study the relationship between gene expressions and clinical outcomes.

A number of samples have arrived in unusable condition because of improper packing. Institutions are reminded to contact the SWOG Tumor Bank by phone to ensure receipt and proper handling. To ensure that snap-frozen specimens do not thaw during overnight transit, the Tumor Bank recommends using a sealed heavy grade styrofoam container at least 1.5 inches thick filled with five pounds of dry ice. Blood samples and frozen samples should not be packed together. Explicit packing instructions are included in section 5.3 of the protocol.


S9431/BIOLOGIC



Total Reg

Oregon Hlth Sci Univ 17 Carilion Medical Ctr/Temple University 1Michigan, U of 16 Kansas City CCOP 1City of Hope Med Ctr 5 Montana CCOP 1Wayne State Univ 5 New Mexico, U of 1Salem Hospital/Oregon Hlth Sci Univ 2 Puget Sound 1Utah, U of 2 South Alabama CCOP 1Wichita CCOP 2 Total (14 Institutions) 56Arizona, U of 1

Patient Characteristics Registrations ending December 31, 2001; Data as of February 27, 2002

Tissues and serum

(n=55) AGE Median 53 .0

Minimum 18 Maximum 79 SEX Males 39

71%

Females 16 29% RACE White (Non-Hispanic) 53

96%

Black (Non-Hispanic) 1 2% American Indian 1 2% SWOG MELANOMA TREATMENT TRIAL S9430 53

96%

other 2 4% PREVIOUSLY REGISTERED TO TREATMENT TRIAL Yes 52

95%

No 3 5% STAGE OF DISEASE AJCC III 3

5%

AJCC IV 52 95% SNAP FROZEN SAMPLE Yes 30

55%

No 25 45% FAMILY HISTORY OF MELANOMA Yes 1

2%

No 54 98% FAMILY HISTORY OF PANCREATIC CANCER Yes 0

0%

No 55 100%


S0008/III

S0008 Phase III Intergroup Coordinating Group: SWOG

Phase III Trial of High Dose Interferon Alfa-2b vs Cisplatin, Vinblastine, DTIC plus IL-2 and Interferon in Patients with High Risk Melanoma

Intergroup Participants: SWOG, CALGB, ECOG

Study Coordinators: L Flaherty, J Thompson, V Sondak, R Tuthill,, J Vetto, J Kirkwood (ECOG), F Haluska (CALGB)




Schema

RANDOMIZE CDDP, VLB, DTIC + IL-2 and IFN Alpha - 2b

1 year High Dose IFN Alpha - 2b

Objectives To compare overall survival and disease-free survival between patients with high risk melanoma who receive high dose interferon alfa-2b versus cisplatin, vinblastine, DTIC plus IL-2 and interferon.

To evaluate the toxicities of these two regimens in this patient population.

Patient Population Patients must have melanoma of cutaneous origin or of unknown primary which fulfill one of the following criteria: an ulcerated primary melanoma with one or more regional lymph node metastases; OR a non-ulcerated melanoma with two or more regional lymph node metastases or one clinically apparent overt, macro-, regional lymph node metastasis (including a single matted nodal mass); OR, any satellite/in-transit metastasis with or without regional lymph node involvment; OR, histologically confirmed:

regional nodal recurrence, recurrent disease in the basin of a previous complete lymphadenectomy, or satellite/in-transit recurrence. Patients are eligible for this trial either at initial presentation of their melanoma or at the time of the first clinically detected recurrent disease. Patients with multiple regional nodal basin involvement are permitted as long as they are the appropriate anatomic drainage basins for the primary site. Gross or microscopic extracapsular nodal extension is permitted. Patients with distant metastases are not eligible.

Patients at initial presentation of melanoma must have adequate wide excision of the primary lesion, if present. Patients with recurrent disease must have all disease completely resected. A full lymphadenectomy is required for all patients. Patients with recurrent disease who have previously undergone a complete lymphadenectomy fulfill this requirement.


S0008/III

Patients must be registered within 56 days of either lymphadenectomy OR surgery to remove all recurrent disease if complete lymphadenectomy has previously been performed. Patients must not have had prior radiotherapy, chemotherapy (including infusion or perfusion therapy), or any immunotherapy with interferon and/or interleukins for any type of cancer.

Patients must be 18 years of age or older, have a Zubrod performance status of 0-1, and have adequate renal, hepatic, hematologic, cardiac, and pulmonary function. Patients must not have autoimmune disorders, conditions of immunosuppression or treatment with corticosteroids. Patients with known AIDS or HIV-1 associated complex or known to be HIV antibody seropositive or hepatitis positive are not eligible for this study.

Stratification/Descriptive Factors Patients are stratified by: newly diagnosed versus recurrent disease.

Newly diagnosed patients are further stratified by the following factors: (1) number of involved nodes: 1-3 vs 4 or more or any matted nodal mass(es) vs satellite/in-transit metastases with no

lymph node involvement; (2) type of lymph node involvement: micrometastases only (including satellite/in-transit metastases) vs any macrometastases; (3) ulceration of the primary: yes vs no vs unknown primary.

Accrual Goals The accrual goal for this study is 410 eligible patients. Interim analyses will be performed when 80% of patients have been accrued and when 2/3 of the anticipated deaths on the control arm have been observed.

Summary Statement As of December 31, 2001, 50 patients have been registered. Eight patients are currently listed as ineligible due to insufficient baseline documentation. CALGB joined the study on July 1, 2001.

Twenty-two eligible patients have been evaluated for toxicity. Four patients on the CVD + Interferon arm have experienced Grade 4 toxicities, which include three cases of neutropenia/granulocytopenia, two cases of leukopenia, and one case each of thrombocytopenia and delusions. One patient on the interferon alone arm experienced a Grade 4 toxicity due to a brain embolism.



Total Reg

ECOG 20 Cleveland Clinic OH 1Wayne State Univ 7 Columbia River CCOP 1Michigan, U of 5 Community Onc Grp/Cleveland Clinic OH 1Greater Phoenix CCOP 4 Grand Rapids CCOP 1City of Hope Med Ctr 2 Puget Sound 1Arizona, U of 1 Salem Hospital/Oregon Hlth Sci Univ 1Arkansas, U of 1 Scripps Clinic/City of Hope Med Ctr 1BAMC/WHMC 1 U of Illinois MBCCOP 1CALGB 1 Total (17 Institutions) 50


S0008/III

Registration, Eligibility, and Evaluability Registrations ending December 31, 2001; Data as of January 17, 2002

TOTAL HD

IFN Alfa-2b CVD

+ IFN/IL-2 NUMBER REGISTERED 50 22 28

INELIGIBLE 8 4 4 Insufficient Documentation 8 4 4 Reversible 8 4 4 ELIG./ PEND. ELIG. 42 18 24 Analyzable, Pend. Elig. 42 18 24 TOXICITY ASSESSMENT Evaluable 22 9 13 Too Early 20 9 11

Patient Characteristics Registrations ending December 31, 2001; Data as of January 17, 2002

HD IFN Alfa-2b

(n=18) CVD + IFN/IL-2

(n=24) AGE Median

50 .5

44 .5

Minimum 27 21 Maximum 71 65 SEX Males

17

94% 19

79%

Females 1 6% 5 21% RACE White (Non-Hispanic)

14

78% 20

83%

Hispanic 1 6% 2 8% Other 3 17% 2 8% DISEASE STATUS New

12

67% 13

54%

Recurrent 6 33% 11 46% FOR NEWLY DIAGNOSED DISEASE (n=12) (n=13) NUMBER OF NODES 1-3

9

75% 10

77%

≥ 4 3 25% 3 23% Satellite/in-transit metastases only 0 0% 0 0% NODAL INVOLVEMENT TYPE Micro or satellite/in-transit metastases

7

58% 10

77%

Macrometastases 5 42% 3 23% ULCERATION no

0

0% 7

54%

yes 8 67% 5 38% unknown primary 4 33% 1 8%


S0008/III

Number of Patients with a Given Type and Degree of Toxicity Registrations ending December 31, 2001; Data as of January 17, 2002

HD IFN Alfa-2b CVD + IFN/IL-2 (n=9) (n=13)

Grade

Grade

TOXICITY 0 1 2 3 4 5 0 1 2 3 4 5 Alkaline phosphatase increase 9 0 0 0 0 0 12 1 0 0 0 0Anemia 9 0 0 0 0 0 12 0 0 1 0 0Anxiety/agitation 9 0 0 0 0 0 12 1 0 0 0 0Bone pain 9 0 0 0 0 0 12 0 0 1 0 0Delusions 9 0 0 0 0 0 12 0 0 0 1 0Headache 8 0 0 1 0 0 12 0 0 1 0 0Hypocalcemia 9 0 0 0 0 0 11 0 0 2 0 0Hypomagnesemia 9 0 0 0 0 0 12 1 0 0 0 0Hypotension 9 0 0 0 0 0 10 0 2 1 0 0Leukopenia 9 0 0 0 0 0 9 0 0 2 2 0Nausea 8 0 0 1 0 0 7 1 1 4 0 0Neutropenia/granulocytopenia 9 0 0 0 0 0 8 1 0 1 3 0SGPT (ALT) increase 8 0 0 1 0 0 13 0 0 0 0 0Sensory neuropathy 9 0 0 0 0 0 12 1 0 0 0 0Syncope 8 0 0 1 0 0 13 0 0 0 0 0Thrombocytopenia 9 0 0 0 0 0 8 1 0 3 1 0Thrombosis/embolism 8 0 0 0 1 0 13 0 0 0 0 0Vomiting 9 0 0 0 0 0 8 2 0 3 0 0 MAXIMUM GRADE ANY TOXICITY Number

5 0 0 3 1 0 2 0 1 6 4 0


S0026/II

S0026 Phase II

Evaluation of Interferon Alfa-2b and Thalidomide in Patients with Disseminated Malignant Melanoma, Phase II

Study Coordinators: L Hutchins, J Clark




Objectives To evaluate the six-month progression-free survival rate of patients with disseminated malignant melanoma when treated with interferon alfa-2b and thalidomide.

To evaluate the confirmed and unconfirmed complete and partial response rate in those patients with measurable disease.

To evaluate the qualitative and quantitative toxicities of interferon alfa-2b and thalidomide administered in a Phase II study.

Patient Population Patients must have histologically proven, surgically incurable Stage IV malignant melanoma. Patients may have measurable or non-measurable disease. Patients with a history of brain metastases are eligible only if they have been resected completely free of disease in the brain and then had whole brain radiation therapy.

All patients must have received at least one prior systemic therapy for Stage IV disease. If all known sites of disease have been previously radiated, there must be clear evidence of progression for the patient to be eligible.

Patients must have adequate renal and liver function, and a Zubrod performance status of 0-2. Patients with known AIDS or HIV-1 associated complex, or known to be HIV antibody seropositive are ineligible. Female patients must not be pregnant or nursing.

Accrual Goals Thirty-five eligible patients will be accrued.

Summary Statement This study was activated on November 1, 2001. As of December 31, 2001, no patients have been registered.


S0116/II

S0116 Phase II

A Phase II Trial of a D1/3-MAGE3-HIS Fusion Protein with Adjuvant SB-AS02B for Patients with Stage IV, M1a or M1b Metastatic Melanoma

Study Coordinators: J Weber, V Sondak, M Disis



Objectives To assess confirmed clinical response rate, estimate the six-month progression-free survival rate, assess qualitative and quantitative toxicities, and measure immune responses in patients with Stage IV, M1a or M1b metastatic melanoma receiving Protein D1/3-MAGE3-His plus adjuvant SB-AS02B.

Patient Population Patients must have histologically documented Stage IV, M1a or M1b, metastatic melanoma that is considered incurable by surgery, radiotherapy, or limb perfusion. Patients must have measurable disease. Patients with metastatic mucosal melanoma are eligible. Patients with a uveal or choroidal primary, or with a history of brain metastases are not eligible.

Patients may have had prior adjuvant therapy. Prior adjuvant isolated limb perfusion is allowed

if there is measurable disease outside the field of the prior limb perfusion. Patients must not have received any prior radiation therapy, chemotherapy, biologic therapy, or any other prior treatment for Stage IV disease. Patients must not have received a previous MAGE-3 peptide or protein vaccine preparation.

Patients must be class I HLA haplotyped prior to registration. Patients must have a Zubrod performance status of 0-2. Patients with AIDS, HIV-1 associated complex, or known to be HIV seropositive, positive for Hepatitis BsAg, or Hepatitis C are not eligible.

Accrual Goals Twenty-five eligible patients will be enrolled initially. If one or more responses are observed, an additional 20 eligible patients will be accrued.

melanoma committee agenda 2002/melanoma.pdfmelanoma. publication status. dr. whitehead s9622...

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