3-AP Plus Cisplatin and Paclitaxel in Treating Patients With Advanced or Metastatic Cancer

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Study Of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine) In Combination With Cisplatin And Paclitaxel In Patients With Advanced And Metastatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00016874
• Other study ID #: VION-CLI-015
• Secondary ID: CDR0000068591AEC
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2001
• Last updated: July 17, 2013
• Start date: December 2000
• Est. completion date: January 2008

Study information

• Verified date: December 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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, cisplatin, and paclitaxel in treating patients who have advanced or metastatic cancer.

Description:

OBJECTIVES:

• Determine the safety and tolerability of 3-AP, cisplatin, and paclitaxel in patients with advanced or metastatic cancer.

• Determine the toxic effects of this regimen in these patients.

• Determine the maximum tolerated dose and recommended phase II dose of this regimen in these patients.

• Determine the pharmacokinetic parameters of this regimen in these patients.

• Determine the tumor response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive 3-AP IV continuously over 96 hours on days 1-4 and paclitaxel IV over 3 hours followed by cisplatin IV over 1 hour on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 1 additional course of therapy after documented CR. Patients with partial response or stable disease may receive therapy for up to 6 months.

Cohorts of 1-6 patients receive escalating doses of 3-AP, paclitaxel, and 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: Approximately 25-30 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed progressive advanced or metastatic cancer

• Failed 1 or more prior standard therapies for disease OR

• Unlikely to respond to any currently available therapies

• Measurable or evaluable disease

• No active CNS metastases

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

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• 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 (occult blood for gastrointestinal cancer allowed)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL

• ALT/AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

• Alkaline phosphatase no greater than 3 times ULN (5 times ULN if liver metastases present)

• Albumin at least 3.0 g/dL

• PT/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, heart block, or uncontrolled congestive heart failure

Pulmonary:

• No moderate to severe compromise in pulmonary function

Other:

• No mental deficits and/or psychiatric history that would preclude study

• No active infection

• No pre-existing severe hearing impairment

• No pre-existing grade 2 or greater neuropathy

• No prior severe allergic reaction to study drugs

• No other life-threatening illness

• No chronic toxic effects from prior chemotherapy greater than grade I

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 18 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Concurrent hematopoietic growth factors allowed except if used prophylactically during first course of study therapy

Chemotherapy:

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered

• More than 6 months since prior combination cisplatin and paclitaxel

• Prior cisplatin or paclitaxel as single agents allowed

• Prior 3-AP allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• More than 3 weeks since prior radiotherapy and recovered

• Concurrent radiotherapy to a single site of progressive disease allowed if site requires treatment within the first course of study therapy

Surgery:

• Not specified

Other:

• More than 3 weeks since any therapy for malignancy and recovered

• No other concurrent investigational drugs without consent of sponsor

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• cisplatin

• paclitaxel

• triapine

Locations

Country	Name	City	State
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Vion Pharmaceuticals

Country where clinical trial is conducted

United States,