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

Sponsor

University Health Network, Toronto (Other)

Overall Status

Completed

CT.gov ID

NCT00072267

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining UCN-01 with topotecan may kill more tumor cells.

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

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer	Drug: 7-hydroxystaurosporine Drug: topotecan hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the antitumor activity of UCN-01 and topotecan, in terms of complete and partial objective response rates, in patients with recurrent, persistent, or progressive advanced ovarian epithelial, primary peritoneal, or fallopian tube cancer.

Secondary

Determine the antitumor activity of this regimen, in terms of stable disease rates and duration of response, in these patients.
Determine the progression-free, median, and overall survival of patients treated with this regimen.
Determine the safety and tolerability of this regimen in these patients.
Determine the relationship between clinical and pharmacodynamic effects of this regimen in these patients.

OUTLINE: This is a 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 up to 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 19-33 patients will be accrued for this study within 5-11 months.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of UCN-01 in Combination With Topotecan in Patients With Advanced Ovarian Cancer

Study Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Apr 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer
Progressive, persistent, or recurrent disease
Measurable disease outside prior radiotherapy field unless disease progression occurred after radiotherapy
Tumor lesions accessible for biopsy
Patients with a medical contraindication to tumor biopsy may be allowed at the discretion of the principal investigator
No more than 2 prior chemotherapy regimens
At least 1 regimen must have contained a platinum agent (i.e., 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 history of coronary artery disease
No symptomatic cardiac dysfunction
No cardiac pathology by electrocardiogram* NOTE: *Patients with symptomatic coronary artery disease must undergo an electrocardiogram

Pulmonary

No symptomatic pulmonary dysfunction

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 8 weeks after study participation
No prior allergic reaction attributed to compounds of similar chemical or biological composition to UCN-01 or other study agents
No insulin-dependent diabetes mellitus
Diabetes controlled by diet or oral hypoglycemic agents allowed at the discretion of the investigator
No other concurrent uncontrolled illness
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior biologic therapy and recovered

Chemotherapy

See Disease Characterisitcs
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No prior topotecan
No other prior topoisomerase I inhibitors

Endocrine therapy

More than 4 weeks since prior hormonal therapy and recovered

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior radiotherapy and recovered
No prior radiotherapy to more than 40% of bone marrow
No prior mediastinal irradiation

Surgery

More than 4 weeks since prior surgery and recovered

Other

No other concurrent anticancer therapy
No other concurrent investigational agents
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	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
4	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9