Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00046917
First received: October 3, 2002
Last updated: February 21, 2014
Last verified: October 2011
  Purpose

Phase I trial to study the effectiveness of combining alvocidib, irinotecan hydrochloride, and cisplatin in treating patients who have advanced solid tumors. 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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: alvocidib
Drug: irinotecan hydrochloride
Drug: cisplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Cisplatin in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD alvocidib when administered in conjunction with irinotecan hydrochloride and cisplatin [ Time Frame: Course 1 ] [ Designated as safety issue: Yes ]
    Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicity (DLT) during the first treatment course. DLT is defined as the occurrence of Grade 4 hematologic toxicity, Grade 3 or 4 non-hematologic toxicity including diarrhea despite antidiarrheal prophylaxis, or any delay in treatment resulting in less than 2 treatments in 3 weeks.


Secondary Outcome Measures:
  • Clinical pharmacokinetics of the regimen [ Time Frame: Week 1 of courses 1 and 2 ] [ Designated as safety issue: Yes ]
  • Therapeutic activity of alvocidib in combination with irinotecan hydrochloride in patients with advanced solid tumors [ Time Frame: After 2 courses of treatment ] [ Designated as safety issue: Yes ]
    Evaluated using Response Evaluation Criteria In Solid Tumors (RECIST).

  • Safety and tolerability [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]
    Evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. Tabulated individually, and summarized by body system, according to dosage of study medication.


Enrollment: 13
Study Start Date: July 2002
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy)
Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride IV over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol (alvocidib), irinotecan (irinotecan hydrochloride), and cisplatin in patients with advanced solid tumors.

II. Determine the clinical pharmacokinetics of this regimen in these patients. III. Determine, preliminarily, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients are stratified according to the number of prior treatment regimens (0 or 1 vs more than 1). Patients receive irinotecan hydrochloride intravenously (IV) over 30 minutes followed immediately by cisplatin IV over 30 minutes followed 7 hours later by alvocidib IV over 1-4.5 hours weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of cisplatin, alvocidib, and irinotecan hydrochloride until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated at the recommended phase II dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists
  • Evaluable disease
  • No previously untreated CNS metastasis
  • No primary CNS tumors
  • Performance status - Karnofsky 60-100%
  • Performance status - ECOG 0-2
  • Not specified
  • WBC at least 3,000/mm^3
  • Neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 2.0 mg/dL
  • AST and ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 60 mL/min
  • No cardiac arrhythmia
  • No congestive heart failure
  • No myocardial infarction within the past 6 months
  • HIV negative
  • No neuropathy grade 2 or greater
  • No serious or uncontrolled infection
  • No other medical condition or reason that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 2 months after study participation
  • At least 4 weeks since prior immunotherapy
  • At least 1 week since prior irinotecan and cisplatin alone
  • At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • Not specified
  • At least 4 weeks since prior radiotherapy
  • Not specified
  • Recovered from all prior therapy
  • No concurrent vitamins, antioxidants, or herbal supplements except a daily multivitamin
  • No other concurrent investigational drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00046917

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Manish Shah Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00046917     History of Changes
Obsolete Identifiers: NCT01645462
Other Study ID Numbers: NCI-2009-00023, NCI-2009-00023, NCI-5700, CDR0000257034, MSKCC-02043, 02-043A, 5700, P30CA008748, R01CA067819, U01CA069856
Study First Received: October 3, 2002
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Irinotecan
Alvocidib
Cisplatin
Camptothecin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014