Clinical trial NCT00072267: UCN-01 and Topotecan in Treating Patients With Recurrent, Persistent, or Progressive Advanced Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
Official title: A Phase II Study of UCN-01 in Combination With Topotecan in Patients With Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
primary peritoneal cavity cancer
fallopian tube cancer
stage III ovarian epithelial cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-11-06
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Margaret and Charles Juravinski Cancer Centre
name: Hal W. Hirte, MD, FRCP(C)
role: PRINCIPAL_INVESTIGATOR
References: