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

A Phase II Evaluation Of Triapine (NCI-Supplied Agent: NSC #663249, IND #68338) In Combination With Cisplatin (Commercially Available: NSC # 119875) In The Treatment Of Recurrent Or Persistent Platinum-Resistant Ovarian Or Primary Peritoneal Carcinoma

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

Study Overview

• Status: Completed
• Conditions: Stage IV Ovarian Epithelial Cancer; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: triapine; Drug: cisplatin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (triapine and cisplatin); 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.	Other: laboratory biomarker analysis; Correlative studies; Drug: triapine; Given IV; Other Names: 3-AP; OCX-191; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency and duration of objective response assessed using RECIST criteria	Up to 5 years
Frequency and severity of observed adverse effects assessed using CTCAE version 3.0	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of progression-free survival	From study entry until disease recurrence, death or date of last contact, assessed up to 5 years
Duration of overall survival	From study entry to death or date of last contact, assessed up to 5 years
Prognostic variables (e.g., initial performance status, age, and mucinous [or clear cell] histology)	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lydia Usha, Gynecologic Oncology Group

Publications and helpful links

General Publications

• Kunos C, Radivoyevitch T, Abdul-Karim FW, Fanning J, Abulafia O, Bonebrake AJ, Usha L. Ribonucleotide reductase inhibition restores platinum-sensitivity in platinum-resistant ovarian cancer: a Gynecologic Oncology Group Study. J Transl Med. 2012 Apr 27;10:79. doi: 10.1186/1479-5876-10-79.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: April 7, 2004
• First Submitted That Met QC Criteria: April 7, 2004
• First Posted (Estimate): April 8, 2004

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Recurrence; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NCI-2012-02585; U10CA027469 (U.S. NIH Grant/Contract); GOG-0126O; CDR0000360854 (Registry Identifier: PDQ (Physician Data Query))