Clinical trial NCT00024323: Combination Chemotherapy in Treating Patients With Advanced Cancer
Official title: A Phase I Study of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine) Administered Daily x 5 in Combination With Cisplatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-06-20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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 with cisplatin in treating patients who have advanced cancer.

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.

Eligibility criteria: 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)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
Study officials:
affiliation: Vion Pharmaceuticals
name: Mario Sznol, MD
role: STUDY_CHAIR
References:
citation: 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.