Clinical trial NCT00045175: UCN-01 and Topotecan in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer
Official title: A Phase I Study of UCN-01 in Combination With Topotecan in Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: primary peritoneal cavity cancer
recurrent ovarian epithelial cancer
fallopian tube cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

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: 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: STUDY_CHAIR
References: