Irofulven in Treating Patients With Recurrent or Persistent Ovarian Epithelial or Primary Peritoneal Cancer

A Phase II Evaluation Of Irofulven (IND #55804, NSC #683863) In The Treatment Of Recurrent Or Persistent Platinium-Sensitive Ovarian Or Primary Peritoneal Cancer

Phase II trial to study the effectiveness of irofulven in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Study Overview

• Status: Completed
• Conditions: Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer
• Intervention / Treatment: Drug: irofulven

Detailed Description

OBJECTIVES:

I. Determine the antitumor activity of irofulven in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal cancer.

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

OUTLINE:

Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

Patients are followed at approximately 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within at least 6 months.

• Study Type: Interventional
• Enrollment (Actual): 61
• 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 to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

  • Recurrent or persistent disease

• At least 1 unidimensionally measurable target lesion* defined as:

  • At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for primary disease

  • Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment
  • Patients who have not received prior paclitaxel may receive a second regimen containing paclitaxel
• Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population)

• Platinum-sensitive disease

  • Platinum-free interval** of more than 6 months, but less than 12 months duration, with no clinical evidence of progressive disease after response to platinum
• Performance status - GOG 0-2 for patients who received 1 prior therapy regimen
• Performance status - GOG 0-1 for patients who received 2 prior therapy regimens
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• Creatinine normal
• Creatinine clearance at least 60 mL/min
• No prior congestive heart failure requiring medication
• No uncontrolled hypertension within the past 6 months
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other invasive malignancies within the past 5 years except nonmelanoma skin cancer
• No history of retinopathy and/or macular degeneration
• No neuropathy (sensory and motor) greater than grade 1
• No active infection requiring antibiotics
• No other illness or condition that would preclude study entry
• No prior bone marrow or stem cell transplantation
• At least 3 weeks since prior biologic therapy or immunotherapy for malignant tumor
• One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule signal transduction inhibitors) allowed
• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered
• No prior irofulven
• No additional prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens
• At least 1 week since prior hormonal therapy for malignant tumor
• Concurrent hormone replacement therapy allowed
• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of marrow-bearing areas
• Recovered from recent prior surgery
• At least 3 weeks since any other prior therapy for malignant tumor
• No prior anticancer treatment that would preclude study therapy
• One prior noncytotoxic cytostatic regimen for recurrent or persistent disease allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment (irofulven); Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.	Drug: irofulven; Given IV; Other Names: 6-hydroxymethylacylfulvene; HMAF; MGI 114; MGI-114

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is disappearance of all target and non-target lesions; Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death.	From entry into study until documented progression or death, assessed up to 5 years.
Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0		Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.	From entry into study to death or date of last contact, assessed up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: January 27, 2003
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (ESTIMATE): January 28, 2003

Study Record Updates

• Last Update Posted (ACTUAL): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Irofulven
• Other Study ID Numbers: NCI-2012-02512 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA027469 (U.S. NIH Grant/Contract); CDR0000269484; GOG-0146O (OTHER: CTEP)