Combination Chemotherapy in Treating Patients With Advanced Cancer

A Phase I Study of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine) Administered Daily x 5 in Combination With Cisplatin

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining 3-AP with cisplatin in treating patients who have advanced cancer.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: cisplatin; Drug: triapine

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of cisplatin when administered with 3-AP in patients with advanced cancer.
• Determine the toxic effects of this regimen in these patients.
• Determine the antitumor responses in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of cisplatin.

Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Arizona Clinical Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed progressive malignant disease that has failed at least 1 conventional treatment or is unlikely to respond to current therapy

• Measurable or evaluable disease

  • Elevated serum tumor marker considered evaluable disease

• No known active CNS metastases

  • Previously treated CNS metastases with no evidence of new CNS metastases allowed if stable for at least 2 months

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL (transfusion allowed)
• No active bleeding or coagulation disorder (except occult blood related to gastrointestinal cancer)

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• ALT and AST no greater than 3 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 5 times ULN
• PT and PTT no greater than 1.5 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No active heart disease
• No myocardial infarction within the past 3 months
• No symptomatic coronary artery disease
• No uncontrolled arrhythmias
• No uncontrolled congestive heart failure

Pulmonary:

• No moderate to severe compromise of pulmonary function

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infectious process
• No pre-existing severe hearing impairment
• No grade 2 or greater neuropathy
• No other life threatening illness
• No prior severe allergic reaction to cisplatin
• No mental deficits and/or psychiatric history that would preclude study
• No persistent chronic toxic effects from prior chemotherapy greater than grade 1

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 2 weeks since prior biologic therapy

Chemotherapy:

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• At least 3 months since prior cisplatin or platinum analogue
• No prior 3-AP

Endocrine therapy:

• At least 2 weeks since prior hormonal therapy

Radiotherapy:

• More than 3 weeks since prior radiotherapy

Surgery:

• At least 3 weeks since prior major surgery and recovered

Other:

• No other concurrent investigational drugs
• No other concurrent nephrotoxic drugs (e.g., aminoglycoside antibiotics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Vion Pharmaceuticals

Publications and helpful links

General Publications

• Kunos CA, Chu E, Beumer JH, Sznol M, Ivy SP. Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies. Cancer Chemother Pharmacol. 2017 Jan;79(1):201-207. doi: 10.1007/s00280-016-3200-x. Epub 2016 Nov 22.

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Study Completion (Actual): June 1, 2003

Study Registration Dates

• First Submitted: September 13, 2001
• First Submitted That Met QC Criteria: June 19, 2003
• First Posted (Estimate): June 20, 2003

Study Record Updates

• Last Update Posted (Estimate): July 18, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: November 1, 2002

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: VION-CLI-021; CDR0000068918 (Registry Identifier: PDQ (Physician Data Query)); NCI-V01-1668