Flavopiridol in Treating Patients With Metastatic Malignant Melanoma

A Phase II Study of Flavopiridol (HMR 1275; NSC 649890) in Patients With Previously Untreated Metastatic Malignant Melanoma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of flavopiridol in treating patients who have metastatic malignant melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Drug: alvocidib

Detailed Description

OBJECTIVES:

• Assess the efficacy of flavopiridol in patients with previously untreated metastatic malignant melanoma.
• Assess the toxicity of this treatment in these patients.
• Assess the time to progression, early progression rate, and response duration in these patients when treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive flavopiridol IV over 1 hour on days 1-3. Treatment continues every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks, and then every 3 months until disease progression or death.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 12-18 months.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center - Calgary
    • Lethbridge, Alberta, Canada, T1J 1W5
      • Lethbridge Cancer Clinic
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 3G6
      • Penticton Regional Hospital
    • Vancouver, British Columbia, Canada, V5Z 3J5
      • Prostate Centre at Vancouver General Hospital
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital - Vancouver
    • Victoria, British Columbia, Canada, V8V 3N1
      • G. Steinhoff Clinical Research
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6ZB
      • Moncton Hospital
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Doctor Leon Richard Oncology Centre
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
      • Newfoundland Cancer Treatment and Research Foundation
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital, Barrie
    • Brampton, Ontario, Canada, L6W 2Z8
      • William Osler Health Centre
    • Hamilton, Ontario, Canada, L8N 1T8
      • Hamilton and Disrict Urology Association
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre
    • Mississauga, Ontario, Canada, L5B 1B8
      • Trillium Health Centre
    • Mississauga, Ontario, Canada, L5M 2N1
      • Credit Valley Hospital
    • Newmarket, Ontario, Canada, L3Y 2P9
      • York County Hospital
    • North York, Ontario, Canada, M2E 1K1
      • North York General Hospital, Ontario
    • Oakville, Ontario, Canada, L6H 3PI
      • Male Health Centre/CMX Research Inc.
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre
    • Peterborough, Ontario, Canada, K9H 7B6
      • Peterborough Oncology Clinic
    • Scarborough, Ontario, Canada, M1P 2V5
      • Scarborough Hospital - General Site
    • St. Catharines, Ontario, Canada, L2R 5K3
      • Hotel Dieu Health Sciences Hospital - Niagara
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre, Sudbury
    • Thunder Bay, Ontario, Canada, P7A 7T1
      • Northwestern Ontario Regional Cancer Centre, Thunder Bay
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Toronto East General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital - Toronto
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5S 1B6
      • Women's College Campus, Sunnybrook and Women's College Health Science Center
    • Toronto, Ontario, Canada, M6R 1B5
      • Saint Joseph's Health Centre - Toronto
    • Weston, Ontario, Canada, M9N 1N8
      • Humber River Regional Hospital
    • Windsor, Ontario, Canada, N8W 2X3
      • Cancer Care Ontario - Windsor Regional Cancer Centre
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
      • Queen Elizabeth Hospital, PEI
  • Quebec
    • Fleurimont, Quebec, Canada, J1H 5N4
      • CHUS-Hopital Fleurimont
    • Joliette, Quebec, Canada, J6E 6J2
      • Centre Hospitalier Régional de Lanaudière
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H2W 1T8
      • Centre Hospitalier de l'Universite' de Montreal
    • Montreal, Quebec, Canada, H2W 1T8
      • Hotel Dieu de Montreal
    • Montreal, Quebec, Canada, H4J 1C5
      • Hôpital du Sacré-Coeur de Montréal
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre Hospitalier Universitaire de Quebec
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint-Sacrament, Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • L'Hopital Laval
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic malignant melanoma not amenable to standard curative therapies

  • No prior regional or systemic therapy for metastatic disease

• Measurable disease

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan
  • Bone lesions not considered measurable
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal:

• Creatinine no greater than ULN

Cardiovascular:

• If history of cardiac disease, ejection fraction greater than 50%
• No clinically significant cardiac symptomology

Pulmonary:

• If history of pulmonary disease, FEV1, FVC, and TLC greater than 60% predicted and DLCO greater than 50% predicted
• No clinically significant pulmonary symptomology

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent serious disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior adjuvant immunotherapy allowed
• No prior immunotherapy for metastatic disease

Chemotherapy:

• No prior chemotherapy for metastatic disease
• No other concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior adjuvant hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• Must have measurable disease outside irradiated area OR
• Evidence of progression or new lesions in irradiated area
• No more than 25% of functioning bone marrow irradiated
• No concurrent radiotherapy to sole site of measurable disease

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No other concurrent anticancer therapy or investigational anticancer agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Susan Burdette-Radoux, MD, McGill Cancer Centre at McGill University

Publications and helpful links

General Publications

• Burdette-Radoux S, Tozer RG, Lohmann RC, Quirt I, Ernst DS, Walsh W, Wainman N, Colevas AD, Eisenhauer EA. Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma. Invest New Drugs. 2004 Aug;22(3):315-22. doi: 10.1023/B:DRUG.0000026258.02846.1c.
• Burdette-Radoux S, Tozer RG, Lohmann R, et al.: NCIC CTG phase II study of flavopiridol in patients with previously untreated metastatic malignant melanoma (IND.137). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1382, 2002.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2000
• Primary Completion (Actual): August 24, 2001
• Study Completion (Actual): December 21, 2009

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: May 20, 2003
• First Posted (Estimate): May 21, 2003

Study Record Updates

• Last Update Posted (Actual): April 9, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Alvocidib
• Other Study ID Numbers: I137; CAN-NCIC-IND137 (Other Identifier: PDQ); NCI-NCIC-137 (Other Identifier: NCI); CDR0000067955 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes