3-AP in Treating Patients With Previously Untreated Locally Recurrent or Metastatic Renal Cell Carcinoma

A Phase II Study of Triapine (NSC 663249) in Previously Untreated Patients With Recurrent Renal Cell Carcinoma

RATIONALE: Drugs used in chemotherapy, such as 3-AP, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 3-AP in treating patients who have locally recurrent or metastatic renal cell (kidney) carcinoma (cancer).

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: triapine

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of 3-AP (Triapine®), in terms of objective response rate, in patients with previously untreated locally recurrent or metastatic renal cell carcinoma.

Secondary

• Determine the adverse events and tolerability of this drug in these patients.
• Determine the time to disease progression and overall survival of patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive 3-AP (Triapine®) IV over 2 hours on days 1-4 and 15-18. Treatment repeats every 28 days for up to 6 courses (for stable patients) in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 1 additional course after documentation of CR. Patients who achieve a partial response (PR) receive 2 additional courses after documentation of stable PR.

Patients are followed every 4 weeks until relapse and then every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1 year.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Margaret and Charles Juravinski Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • Cancer Care Ontario-London Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Toronto Sunnybrook Regional Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2L-4M1
      • Centre hospitalier de l'Université de Montréal

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma

  • Locally recurrent OR metastatic disease
  • Incurable by standard therapy

• Clinically and/or radiologically measurable disease

  • At least 1 unidimensionally measurable lesion* at least 20 mm by x-ray, physical exam, or non-spiral CT scan OR at least 10 mm by spiral CT scan
  • If the sole site of measurable disease is in a previously irradiated field, there must be documented disease progression at that site NOTE: *Bone lesions are not considered measurable disease
• No documented brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No glucose-6-phosphate dehydrogenase (G6PD) deficiency* NOTE: *Screening for G6PD deficiency is required for patients of African, Asian, or Mediterranean descent

Hepatic

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

Renal

• Creatinine no greater than 1.5 times ULN
• Creatinine clearance at least 50 mL/min

Cardiovascular

• No myocardial infarction within the past 6 months
• No symptomatic congestive heart failure
• No unstable angina
• No active cardiomyopathy
• No cardiac arrhythmia
• No uncontrolled hypertension

Pulmonary

• No pulmonary disease requiring oxygen

Immunologic

• HIV negative
• No known hypersensitivity to compounds of similar chemical or biological composition to 3-AP (Triapine®)
• No active uncontrolled or serious infection
• No immunodeficiency

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor with no evidence of disease for at least 5 years
• No history of significant neurologic or psychiatric disorder (e.g., uncontrolled psychotic disorders) that would preclude giving informed consent or complying with study requirements
• No active peptic ulcer disease
• No other serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 3 months since prior interferon for advanced or recurrent disease
• No other prior immunotherapy for advanced or recurrent disease
• No prior gene therapy

Chemotherapy

• No prior systemic chemotherapy for advanced or recurrent disease

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy (except low-dose nonmyelosuppressive radiotherapy) and recovered

Surgery

• At least 2 weeks since prior major surgery

Other

• No prior investigational anticancer agents
• No other concurrent anticancer agents or therapy
• No other concurrent investigational therapy

• No concurrent anticoagulants

  • Concurrent nontherapeutic warfarin or heparin allowed

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
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jennifer Knox, MD, Toronto General Hospital

Publications and helpful links

General Publications

• Knox JJ, Hotte SJ, Kollmannsberger C, Winquist E, Fisher B, Eisenhauer EA. Phase II study of Triapine in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161). Invest New Drugs. 2007 Oct;25(5):471-7. doi: 10.1007/s10637-007-9044-9. Epub 2007 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2004
• Primary Completion (Actual): October 4, 2005
• Study Completion (Actual): September 22, 2008

Study Registration Dates

• First Submitted: January 9, 2004
• First Submitted That Met QC Criteria: January 11, 2004
• First Posted (Estimated): January 12, 2004

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; stage III renal cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: I161; CAN-NCIC-IND161 (Other Identifier: PDQ); CDR0000347409 (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