Ovarian Cancer
Conditions
Keywords
ovarian cancer, bendamustine
Brief summary
The study design is a non-randomized, open label, single center Phase II trial. Eligible patients are women who have a confirmed diagnosis of ovary, fallopian tube cancer or primary peritoneal serous papillary carcinoma who have relapsed or are refractory to therapy after primary treatment of their disease. Patients will be treated with bendamustine Hydrochloride 90 mg/m2 intravenously on days 1(± 1 day) and 2 (± 1 day) every 28 days. If no grade ≥3 hematologic adverse event appears the dose will be escalated to 120 mg/m2 on days 1(± 1 day) and 2 (± 1 day) every 28 days at cycle 2. 20 patients will be enrolled in the study. OBJECTIVES Hypothesis/Rationale: To determine the efficacy and safety of bendamustine hydrochloride, in women with platinum and taxane refractory ovarian cancer.
Detailed description
Bendamustine, a non-cross resistant cytotoxic, has potential to offer a new regimen for the treatment of ovarian cancer in women who are refractory to standard drug regimens. Non-cross resistance to platinum is critical for the development of effective salvage regimens in this platinum resistant population. In addition bendamustine's cytotoxic effects are thought to occur via several mechanistic pathways, apoptosis, DNA repair, DNA replication, DNA transcription. The study seeks to determine the efficacy and safety of bendamustine in women with advanced ovarian cancer.
Interventions
DRUGBendamustine HCL
bendamustine HCL 90 mg/m2 intravenously on days 1(± 1 day) and 2 (± 1 day) every 28 days. If no grade ≥3 hematologic adverse event appears the dose will be escalated to 120 mg/m2 on days 1(± 1 day) and 2 (± 1 day) every 28 days at cycle 2.
Sponsors
Cephalon
University of Arizona
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Patients must have histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary, fallopian tube cancer or primary peritoneal serous papillary carcinoma. Borderline ovarian tumors are not allowed. 2 Patients must have relapsed within 6 months of completing, or had a best response of increasing disease during any number of prior chemotherapy regimens with a platinum (either cisplatin or carboplatin) and a taxane (paclitaxel or docetaxel). These agents may have been administered concurrently or sequentially. Any number of additional regimens for recurrent disease will be allowed, as long as the patient performance status is 0-2 Gynecologic Oncology Group (GOG). 3 Patients must have measurable or evaluable (i.e. positive serum Cancer Antigen (CA) -125 marker) disease. Scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration. Scans or ultrasounds for non -measurable disease must have been performed within 28 days prior to registration. 4 Prior radiation is allowed as long as it encompassed no more than 25% of the bone marrow. Debulking surgery for relapsed disease is allowed as long as the patient has measurable or evaluable disease remaining after the surgery. Patient must have recovered from all side effects of surgery. 5 Patients must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to registration. Patients must not have had a major surgery within 14 days prior to registration. 6 Patients must have a GOG performance status of 0-2. 7 Patients must have adequate liver function as defined by a serum bilirubin ≤2.0 x the institutional upper limit of normal (IULN), serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) ≤2.5 x the institutional upper limit of normal obtained within 14 days prior to registration. 8 Patients must have an adequate renal function as defined by a serum creatinine ≤1.5x the institutional upper limit of normal obtained within 14 days prior to registration 9 Patients must not have Class 3 /4 cardiac problems as defined by the New York Heart Association Criteria (e.g., congestive heart failure, myocardial infarction within 2 months of study) 10 Patients must not be pregnant or nursing as bendamustine maybe harmful to the developing fetus and newborn. Women of reproductive potential must have a negative serum pregnancy test within 7 days prior to registration. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug. 11 No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years. 12 Patients must have the following hematological criteria: Hemoglobin of ≥9gm/dL White blood cell count ≥ 2500 Platelets ≥ 100,000 13 Patients must be ≥ 18 years of age. \-
Exclusion criteria
1. No borderline ovarian tumors and mixed mesodermal soft tissue sarcomas 2. No psychological, familial, sociological, or geographical conditions that do not permit medical follow-up or compliance with the study protocol 3. Except for cancer-related abnormalities, patients should not have unstable or preexisting major medical conditions 4. No medical life-threatening complications of their malignancies 5. No known severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, active uncontrolled infection, or HIV) 6. Inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 and/or diastolic blood pressure ≥100 mmHg on antihypertensive medications) 7. New York Heart Association (NYHA) Grade III or greater congestive heart failure 8. Evidence of 5 to ≤10% loss of weight from baseline (baseline defined as the screening weight taken approximately 14 days of Day 0) that is not related to ascites or paracentesis. 9. Evidence of uncontrollable nausea 10. Presence of central nervous system or brain metastases 11. Known hypersensitivity to any component of bendamustine HCL \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment. | life of the study | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria or Cancer Antigen (CA)125 response using the modified Gynecologic Cancer Intergroup(GCIG) criteria |
| Overall Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment. | Life of study | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicities of Patients Treated With Bendamustine. | Life of the study | Grade 4 Toxicity |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bendamustine bendamustine HCL 90 mg/m2 intravenously on days 1(± 1 day) and 2 (± 1 day) every 28 days. If no grade ≥3 hematologic adverse event appears the dose will be escalated to 120 mg/m2 on days 1(± 1 day) and 2 (± 1 day) every 28 days at cycle 2. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Bendamustine |
|---|---|
| Age, Continuous | 58 years |
| Cell Type Clear Cell | 1 Participants |
| Cell Type Endometrioid | 3 Participants |
| Cell Type Serous | 6 Participants |
| Eastern Cooperative Oncology Group performance status 0 | 9 Participants |
| Eastern Cooperative Oncology Group performance status 1 | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Median number of prior regimens | 5 Regimens |
| Primary Site Ovarian | 9 participants |
| Primary Site Peritoneal | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor Grade 2 | 2 Participants |
| Tumor Grade 3 | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
Overall Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment.
Time frame: Life of study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bendamustine Median Progression Free Surivial in Months | Overall Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment. | 393 Days |
Primary
Progression Free Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria or Cancer Antigen (CA)125 response using the modified Gynecologic Cancer Intergroup(GCIG) criteria
Time frame: life of the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bendamustine Median Progression Free Surivial in Months | Progression Free Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment. | 140 Days |
Secondary
Toxicities of Patients Treated With Bendamustine.
Grade 4 Toxicity
Time frame: Life of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bendamustine Median Progression Free Surivial in Months | Toxicities of Patients Treated With Bendamustine. | 0 Partcipants |