Polyglutamate Camptothecin in Treating Patients With Advanced Cancer

Phase I Study of CT-2106 in Patients With Advanced Malignancy

RATIONALE: Drugs used in chemotherapy such as polyglutamate camptothecin may be able to deliver the drug directly to tumor cells while leaving normal cells undamaged.

PURPOSE: Phase I trial to study the effectiveness of polyglutamate camptothecin in treating patients who have advanced cancer.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: polyglutamate camptothecin

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of polyglutamate camptothecin (CT-2106) in patients with advanced malignancies.
• Determine the tolerability of this drug in these patients.
• Determine the safety of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the disease response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive polyglutamate camptothecin (CT-2106) IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients receive 2 additional courses beyond confirmation of complete response.

Cohorts of 3-6 patients receive escalating doses of CT-2106 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.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A total of 12-48 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering 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 advanced malignancy
• No active brain metastases (as indicated by clinical symptoms, cerebral edema, or progressive tumor growth) that have been unstable for at least 8 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine no greater than 1.5 times ULN
• No history of hemorrhagic cystitis
• No history of microscopic hematuria associated with drug therapy or radiotherapy or of unknown origin

Cardiovascular

• No significant cardiac disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to comply with study schedule and assessments
• No other significant nonmalignant systemic disease
• No active infection
• No other condition that would in the investigator's opinion make the patient an inappropriate study candidate

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 3 prior chemotherapy regimens
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior definitive radiotherapy (except for palliative reasons to sites of nonmeasurable disease, in patients with measurable disease at baseline)
• Concurrent palliative radiotherapy allowed

Surgery

• More than 4 weeks since prior major thoracic or abdominal surgery

Other

• Recovered from prior therapy (except alopecia or stable grade 1 neuropathy)
• More than 4 weeks since prior investigational agents
• No prior myeloablative therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jakob Dupont, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• McNamara MV, Doroshow JH, Dupont J, et al.: Preliminary pharmacokinetics of CT-2106 (polyglutamate camptothecin) in patients with advanced malignancies. [Abstract] J Clin Oncol 22 (Suppl 14): A-2073, 145s, 2004.
• Springett GM, Takimoto C, McNamara M, et al.: Phase I study of CT-2106 (polyglutamate camptothecin) in patients with advanced malignancies. [Abstract] J Clin Oncol 22 (Suppl 14): A-3127, 226s, 2004.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: May 6, 2003
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: April 1, 2005

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Camptothecin
• Other Study ID Numbers: CTI-PGC101; MSKCC-03002; CDR0000298987 (Registry Identifier: PDQ (Physician Data Query))