UCN-01 and Topotecan in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase I Study of UCN-01 in Combination With Topotecan in Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045175
• Other study ID #: PMH-PHL-005
• Secondary ID: CDR0000256917NCI
• Status: Completed
• Phase: Phase 1
• First received: September 6, 2002
• Last updated: June 21, 2016
• Start date: June 2002

Study information

• Verified date: June 2016
• Source: University Health Network, Toronto
• 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. Topotecan may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy with topotecan may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with topotecan in treating patients who have recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and topotecan in patients with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer.

• Determine the safety and tolerability of this regimen in these patients.

• Determine the relationship between clinical and pharmacokinetic effects of this regimen in these patients.

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

Patients receive UCN-01 IV over 3 hours on day 1 and topotecan IV over 30 minutes on days 1-5. Treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 and topotecan until the maximum tolerated dose (MTD) 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. Up to 12 additional ovarian epithelial cancer patients are then treated at the recommended phase II dose.

Patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 6-10 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed recurrent ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer

• Measurable disease outside of field of prior radiotherapy OR

• Progressive disease within field after radiotherapy

• Must have had no more than 2 prior chemotherapy regimens

• At least 1 prior regimen must have included a platinum agent (e.g., carboplatin or cisplatin)

• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR

• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

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

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)

• AST/ALT no greater than 2.5 times ULN

Renal

• Creatinine no greater than ULN OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No coronary artery disease

• No symptomatic cardiac dysfunction

• No symptoms suggestive of coronary artery disease with evidence of cardiac pathology

Pulmonary

• No symptomatic pulmonary dysfunction

Other

• No prior allergic reaction attributed to compounds of similar chemical or biologic composition to UCN-01 or other agents used in this study

• No insulin-dependent diabetes mellitus

• No other uncontrolled concurrent illness

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study compliance

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior biologic therapy

Chemotherapy

• See Disease Characteristics

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• No prior topotecan (other prior topoisomerase I inhibitors allowed)

Endocrine therapy

• At least 4 weeks since prior hormonal therapy

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy

• No prior radiotherapy to more than 40% of bone marrow

• No prior mediastinal irradiation

Surgery

• At least 4 weeks since prior surgery

Other

• Recovered from all prior therapy

• No other concurrent investigational agents

• No other concurrent anticancer agents or therapies

• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Peritoneal Neoplasms
• Primary Peritoneal Cavity Cancer

Intervention

Drug:
• 7-hydroxystaurosporine

• topotecan hydrochloride

Locations

Country	Name	City	State
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada,