3-AP and Cisplatin in Treating Patients With Recurrent or Persistent Platinum-Resistant Ovarian Epithelial or Primary Peritoneal Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage III Ovarian Epithelial Cancer; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

Treatments: Other: laboratory biomarker analysis; Drug: triapine; Drug: cisplatin

Study type: Interventional

Funder types: NIH

Identifiers

NCT00081276

U10CA027469 (U.S. NIH Grant/Contract)

GOG-0126O

NCI-2012-02585

CDR0000360854 (Registry Identifier)

Details and patient eligibility

About

Drugs used in chemotherapy, such as 3-AP and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. This phase II trial is studying how well giving 3-AP together with cisplatin works in treating patients with recurrent or persistent platinum-resistant ovarian epithelial cancer or primary peritoneal cancer

Full description

PRIMARY OBJECTIVES:

I. Determine the antitumor activity of 3-AP and cisplatin in patients with recurrent or persistent platinum-resistant ovarian epithelial or primary peritoneal cancer.

II. Determine the toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of progression-free survival and overall survival in patients treated with this regimen.

II. Determine the effects of prognostic variables, including initial performance status, age, and mucinous (or clear cell) histology, in these patients.

OUTLINE: This is a non-randomized study.

Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total of 23-48 patients will be accrued for this study within 13 months.

Enrollment: 48 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed ovarian epithelial or primary peritoneal cancer

  • Recurrent or persistent disease

• At least 1 unidimensionally measurable target lesion

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
  • Outside a previously irradiated field

• Received 1 prior platinum-based chemotherapy regimen (e.g., carboplatin, cisplatin, or other organoplatinum compound) for primary disease

  • Initial treatment may have included high-dose, consolidation, or extended therapy after surgical or non-surgical assessment

• Considered platinum resistant or refractory, according to 1 of the following criteria:

  • Treatment-free interval of less than 6 months after platinum-based therapy
  • Disease progression during platinum-based therapy

• Ineligible for any higher priority GOG protocol

• Performance status - GOG 0-2 (for patients who received 1 prior treatment regimen)

• Performance status - GOG 0-1 (for patients who received 2 prior treatment regimens)

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)

• Bilirubin ≤ 1.5 times ULN

• Creatinine ≤ 1.5 times ULN

• No serious cardiac disease

• No prior myocardial infarction

• No uncontrolled congestive heart failure

• No pulmonary disease requiring oxygen

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Neuropathy (sensory and motor) ≤ grade 1

• No active infections requiring antibiotics

• No hearing impairment

• No known G6PD deficiency

• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

• At least 3 weeks since prior biologic or immunologic agents for malignant tumor

• One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) allowed

• See Disease Characteristics

• One prior paclitaxel-containing regimen allowed

• No prior 3-AP

• No other prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens

• Recovered from prior chemotherapy

• At least 1 week since prior hormonal therapy for malignant tumor

• Concurrent hormone replacement therapy allowed

• No prior radiotherapy to more than 25% of marrow-bearing areas

• Recovered from prior radiotherapy

• Recovered from prior surgery

• No prior cancer therapy that contraindicates receiving study therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

48 participants in 1 patient group

Treatment (triapine and cisplatin)

Experimental group

Description:

Patients receive 3-AP IV over 2 hours on days 1-4 and cisplatin IV over 1 hour on days 2 and 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: cisplatin

Other: laboratory biomarker analysis

Drug: triapine