SJG-136 in Treating Patients With Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer That Did Not Respond to Previous Treatment With Cisplatin or Carboplatin

NCT ID: NCT01200797

Last Updated: 2015-05-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2013-02-28

Brief Summary

This phase II trial is studying how well SJG-126 works in treating patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer that did not respond to previous treatment with cisplatin or carboplatin. Drugs used in chemotherapy, such as SJG-136, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the overall response rate to SJG-136 in patients with persistent or recurrent platinum-refractory epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

II. To assess the nature and degree of toxicity of this regimen in these patients.

III. To determine other parameters of response, including progression-free survival, overall survival, and time to progression in patients treated with this regimen.

Correlative Endpoints:

I. To correlate response rates with the degree of DNA adduct formation in peripheral blood mononuclear cells (PBMCs) and tumor cells as measured by the single-cell gel electrophoresis (Comet) assay and γ-H2AX assay.

II. To assess whether the rate of DNA adduct formation in PBMCs correlates with the rate of DNA adduct formation in tumor cells.

III. To evaluate BRCA1 protein expression in archival tissue specimens from the patient's primary tumor reductive surgery.

IV. To determine the ability of BRCA1 protein in repairing/removing DNA-adducts in PBMCs and tumor tissue.

VI. To evaluate the effect of BRCA1 protein expression on the overall response rate to SJG-136.

OUTLINE: This is a multicenter study.

Patients receive SJG-136 IV over 20 minutes on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection at baseline and periodically during study for correlative studies. Tumor tissue samples may also be collected.

After completion of study therapy, patients are followed up for 30 days and then annually thereafter.

Conditions

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (SJG-136)

Patients receive SJG-136 IV over 20 minutes on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

SJG-136

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

SJG-136

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Must have persistent or recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma, with histologic confirmation of the original primary tumor.
• Must have had at least one prior platinum-based (cisplatin or carboplatin) chemotherapy regimen for the management of their primary disease. This would include intraperitoneal chemotherapy.
• Must be considered platinum refractory or resistant, defined as patients with progression of disease during platinum-based chemotherapy, patients having persistent disease at the completion of platinum-based chemotherapy, or patients having a disease free interval following prior platinum therapy of less than six months.
• May have had no more than three prior treatment regimens for their epithelial ovarian, primary peritoneal or fallopian tube carcinoma. Consolidation or maintenance therapy initiated within six weeks of the completion of primary therapy will not be counted as an additional regimen.
• Must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• Time interval from last chemotherapy, radiotherapy, or surgery of at least four weeks and the patient must have recovered from any significant adverse effects of prior treatment. Patients must be at least six weeks from having received nitrosoureas or mitomycin C.
• Life expectancy greater than three months.
• Must have adequate bone marrow and organ function:

• Leukocyte count > 3 x 10^9/L
• Absolute neutrophil count (ANC) > 1.5 x 10^9/L
• Platelet count > 100 x 10^9/L
• Total bilirubin Within normal institutional limits
• Aspartate aminotransferase (AST)/alanine transaminase (ALT) < 2.5 x institutional upper limits of normal
• Creatinine < 1.5 mg/dL or calculated creatinine clearance (ClCr) > 60 ml/min by Cockcroft Gault method, as below. ClCr = weight (kg) x (140-age) x 0.85 72 x serum creatinine (mg/dL)
• Participants must have signed an approved informed consent.
• Participants of childbearing potential must have a negative serum pregnancy test prior to study entry and must use an effective form of contraception.
• Must have archival tissue available from their original tumor debulking surgery for assessment of BRCA1 protein expression.

Exclusion Criteria

• Patients with borderline ovarian tumors, ovarian germ cell tumors, ovarian sex-cord stromal tumors, or other non-epithelial ovarian tumors are not eligible.
• Patients receiving any other investigational agents.
• Patients who have received radiation therapy to more than 25% of the bone marrow.
• Patients who have previously received SJG-136 or related compounds.
• Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with the study requirements.
• Prior malignancy (other than cervical carcinoma in situ, ductal carcinoma in situ of the breast, or non-melanoma skin cancer) unless treated with curative intent and without evidence of disease for three years.
• With the exception of alopecia (or other situations in which the organ dysfunction or symptoms are considered clinically insignificant or irrelevant to the study), patients may not have baseline organ dysfunction or symptoms that qualify as grade 2 or higher by the CTEP Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0. Particular attention should be paid to assessment of pre-existing edema, since vascular leak syndrome was the dose limiting toxicity of this agent in the phase I trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marta Crispens

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

Hartford Hospital

Hartford, Connecticut, United States

Oncology Associates PC

Hartford, Connecticut, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Countries

United States

Other Identifiers

NCI-2011-02519

Identifier Type: REGISTRY

Identifier Source: secondary_id

MCC-VICC-GYN-1003

Identifier Type: -

Identifier Source: secondary_id

CDR0000682791

Identifier Type: -

Identifier Source: secondary_id

VICC GYN 1003

Identifier Type: OTHER

Identifier Source: secondary_id

8489

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00100

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02519

Identifier Type: -

Identifier Source: org_study_id

NCT01199796

Identifier Type: -

Identifier Source: nct_alias