Open Trial of Bendamustine Hydrochloride in Women With Advanced Ovarian Cancer

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT00867503
• Collaborator: Cephalon (Industry)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 49.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Bendamustine HCL	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Phase II Trial of Bendamustine Hydrochloride (HCL) in Women With Advanced Ovarian Cancer
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Bendamustine 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.; Other Names: bendamustine hydrochloride

Outcome Measures

Primary Outcome Measures

1. 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

2. 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 Outcome Measures

1. Toxicities of Patients Treated With Bendamustine. [Life of the study]

   Grade 4 Toxicity

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724

Sponsors and Collaborators

• University of Arizona
• Cephalon

Investigators

• Principal Investigator: Setsuko K Chambers, MD, University of Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Arizona
• ClinicalTrials.gov Identifier: NCT00867503
• Other Study ID Numbers: 08-1137-04
• First Posted: Mar 23, 2009
• Last Update Posted: Jul 24, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by University of Arizona: ovarian cancer; bendamustine
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Bendamustine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Bendamustine
Arm/Group Description	Bendamustine Hydrochloride (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.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Bendamustine
Arm/Group Description	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.
Overall Participants	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	10 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 50%
Not Hispanic or Latino	5 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%
Primary Site (participants) [Number]
Ovarian	9 90%
Peritoneal	1 10%
Median number of prior regimens (Regimens) [Median (Full Range) ]
Median (Full Range) [Regimens]	5
Eastern Cooperative Oncology Group performance status (Number) [Number]
0	9 90%
1	1 10%
Tumor Grade (Number) [Number]
2	2 20%
3	8 80%
Cell Type (Number) [Number]
Serous	6 60%
Endometrioid	3 30%
Clear Cell	1 10%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival in Patients With Platinum and Taxane Refractory Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer With Bendamustine Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bendamustine Median Progression Free Surivial in Months
Arm/Group Description	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.
Measure Participants	10
Median (Full Range) [Days]	140

2. Secondary Outcome

Title	Toxicities of Patients Treated With Bendamustine.
Description	Grade 4 Toxicity
Time Frame	Life of the study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bendamustine Grade 4 Toxicity
Arm/Group Description	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.
Measure Participants	10
Number [Partcipants]	0

3. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Median Overall Survival in Days
Arm/Group Description	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.
Measure Participants	10
Median (Full Range) [Days]	393

Adverse Events

Time Frame	Life of study
Arm/Group Title	Bendamustine
Arm/Group Description	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.
All Cause Mortality
	Bendamustine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bendamustine
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Gastrointestinal disorders
Small Bowel Obstruction	2/10 (20%)	4
Abdominal Pain	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Bendamustine
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Leukocytes	6/10 (60%)
Neutrophils	5/10 (50%)
Hemoglobin	5/10 (50%)
Platlets	5/10 (50%)
Cardiac disorders
Hypotension	1/10 (10%)
Gastrointestinal disorders
Constipation	2/10 (20%)
Diarrhea	1/10 (10%)
Other GI	2/10 (20%)
General disorders
Fatigue	4/10 (40%)
Fever	3/10 (30%)
Rigors	2/10 (20%)
Weight Loss	1/10 (10%)
Dehydration	1/10 (10%)
Distention	1/10 (10%)
Dysgeusia	3/10 (30%)
Nausea	6/10 (60%)
Oral Mucositis	2/10 (20%)
Vomiting	5/10 (50%)
Dizziness	2/10 (20%)
Sensory Neuropathy	2/10 (20%)
Pain Abdominal, chest, back	3/10 (30%)
Headache	1/10 (10%)
COugh/Dyspnea	2/10 (20%)
Infections and infestations
Cellulitis	1/10 (10%)
Metabolism and nutrition disorders
Creatinine	1/10 (10%)
Hyperbilirubinemia	1/10 (10%)
Hypokalemia	1/10 (10%)
Hypoantremia	1/10 (10%)
Musculoskeletal and connective tissue disorders
Muscle weakness/ Cramping	2/10 (20%)
Psychiatric disorders
Anoxeria	2/10 (20%)
Skin and subcutaneous tissue disorders
Pruritus	1/10 (10%)
Other	1/10 (10%)

Limitations/Caveats

The team was not able to collect fresh tumor tissue at the time of the study, so we could not examine patient tumors to determine their DNA repair capabilities.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.