Brief Title
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall Response (OR)
Condition
Recurrent Fallopian Tube Cancer
Intervention
SJG-136
Study Arms / Comparison Groups
Treatment (SJG-136)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
19
Start Date
July 2010
Completion Date
February 2013
Primary Completion Date
October 2012
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.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Marta Crispens, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01200797
Organization ID
NCI-2011-02519
Secondary IDs
NCI-2011-02519
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Marta Crispens, Principal Investigator, H. Lee Moffitt Cancer Center and Research Institute
Verification Date
May 2015