Clinical trial NCT01200797: 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
Official title: A Phase II Evaluation of SJG-136 in Women With Cisplatin-Refractory or Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-09-14
Enrollment: 19
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Response (OR)
timeFrame: On-treatment date to date of disease progression (assessed up to 12 months)
measure: Number of Patients With Each Worst-grade Toxicity
timeFrame: On-study date to 30 days following final dose of study
measure: Progression-free Survival (PFS)
timeFrame: On-study date to lesser of date of progression or date of (assessed up to 12 months)
measure: Overall Survival (OS)
timeFrame: On-study date to date of death from any cause (assessed up to 12 months)
measure: Time to Progression (TTP)
timeFrame: On-study date to date of progression (assessed up to 12 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Hartford
country: United States
facility: Oncology Associates PC
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Marta Crispens
role: PRINCIPAL_INVESTIGATOR
References: