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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT00045175

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer	Drug: 7-hydroxystaurosporine Drug: topotecan hydrochloride	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2002

Actual Primary Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UCN-01 in combination with topotecan	Drug: 7-hydroxystaurosporine Drug: topotecan hydrochloride

Arm

Intervention/Treatment

Experimental: UCN-01 in combination with topotecan

Drug: 7-hydroxystaurosporine

Drug: topotecan hydrochloride

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
2	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
3	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9