A Study of Carboplatin and DOXIL Plus Bevacizumab in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancers

Ovarian Neoplasms Clinical Trial

Official title:

A Phase II Single Arm Study of Carboplatin and DOXIL (PLD) Plus Bevacizumab in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00698451
• Other study ID #: CR015094
• Secondary ID: DOXILOVC2007
• Status: Completed
• Phase: Phase 2
• First received: June 12, 2008
• Last updated: August 20, 2013
• Start date: August 2008
• Est. completion date: October 2010

Study information

• Verified date: August 2013
• Source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the response rate (Complete Response (CR) and Partial Response (PR)) to carboplatin and DOXIL treatment in combination with bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube and primary peritoneal cancers. All patients will received DOXIL, carboplatin and bevacizumab for a maximum of ten 28-day cycles. Patients will be followed for six months following treatment to assess progression-free survival.

Description:

DOXIL pegylated liposomal doxorubicin (PLD) is approved for use in patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy. Data suggest that combination therapy of carboplatin plus DOXIL provides superior benefit to single agent therapy. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is approved for use in combination with intravenous 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer and in combination with carboplatin and paclitaxel (treatment of non-small cell lung cancer); and with paclitaxel (first line treatment of metastatic HER2-negative breast cancer). There are data showing bevacizumab has activity in the treatment of ovarian cancer, and it is currently being studied in platinum-sensitive relapsed ovarian cancer in combination with carboplatin/gemcitabine. No data exist on the efficacy and safety of bevacizumab administered with carboplatin and DOXIL. Based on the growing interest of incorporating bevacizumab in to ovarian cancer treatment and the activity seen to date, the evaluation of the combination of carboplatin and DOXIL with bevacizumab is warranted. This is a single arm (one dosing regimen), multicenter, open label (both the patient and the physician know what drug is being given) study in patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancers. This study will be conducted in multiple sites across the United States. All patients will receive DOXIL, carboplatin and bevacizumab by intravenous (IV) infusion for a maximum of ten (10) 28-day cycles. A disease response assessment will occur after the completion of Cycles 2, 4, 6, 8 and at the end of treatment. Patients will be followed for six (6) months post-treatment for progression-free survival. Disease progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST). RECIST is an accepted classification for response to treatment with classifications of Complete Response (CR), Partial Response( (PR), Progressive Disease (PD) or Stable Disease (SD).The primary objective of this study is to evaluate the objective response rate (Complete Response (CR) and Partial Response (PR)) to carboplatin and DOXIL treatment in combination with bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube and primary peritoneal cancers. The secondary objectives are to assess the safety profile of carboplatin and DOXIL in combination with bevacizumab as well as the following efficacy endpoints: Duration of response, Progression-free Survival, and Time to Progression. Safety will be evaluated using adverse events, clinical laboratory tests, and tests for cardiac function after the first 20 patients have been entered and received at least 2 cycles of therapy. Overall safety will be summarized at study completion. DOXIL (30 mg/m2), and carboplatin (area under the curve (AUC 5)) will be given on Day 1 of each 28-day cycle. Bevacizumab (10 mg/kg) will be given on days 1 and 15 of every 28-day cycle. All treatment will be given by intravenous (IV) infusion and repeated every 4 weeks for up to 10 cycles.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic diagnosis of epithelial ovarian, fallopian tube or primary peritoneal cancer

• Relapse-free interval of >6 months afer completion of first line platinum-based chemotherapy

• Measurable disease (at least one lesion that can be accurately measured in a least 1 dimension)

• Adequate bone marrow function, renal, and liver function. Normal cardiac function

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria:

• No patients who have received more than 1 previous regimen of chemotherapy (maintenance is not considered a second regimen)

• No patients receiving immunotherapy or radiotherapy or patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis

• No patients who require parenteral hydration or nutrition or have clinical signs or symptoms of gastrointestinal bowel obstruction or perforation

• No patients with previous or current malignancy other than basal cell or squamous cell carcinoma of the skin

• No patients with clinically significant cardiovascular disease

• No patients with a history of bevacizumab or other VEGF or VEGF receptor-targeted agent use.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fallopian Tube Neoplasms
• Neoplasms
• Ovarian Neoplasms
• Peritoneal Neoplasms

Intervention

Drug:
• doxorubicin HCL liposome; bevacizumab; carboplatin
30 mg/m2 by intravenous infusion Day 1 of each 28 day cycle; 10 mg/kg by intravenous infusion Days 1 and 15 of each 28 day cycle; AUC=5 by intravenous infusion Day 1 of each 28 day cycle

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Centocor Ortho Biotech Services, L.L.C.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Efficacy End Point is the Number of Patients With an Objective Response.	Objective Response Rate to Treatment is defined as the Proportion of Patients With a Complete Response (CR) or Partial Response (PR). A Complete Response (CR) is the disappearance of all target lesions and a Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD	Approximately 280 days (from start of treatment to the end of 10 cycles of treatment where each cycle is 28 days)	Yes
Secondary	The Secondary Efficacy Endpoints is Duration of Objective Response.	Objective Response Rate to Treatment Defined as the Proportion of Patients With a Complete Response (CR) or Partial Response (PR) Where a Complete response (CR) is the disappearance of all target lesions and a Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Duration of response: Duration of response was defined only for subjects with CR or PR as the best overall response. It was calculated from the date of first documentation of response to the date of disease progression or death due to progressive disease.	Duration of response was defined only for subjects with CR or PR as the best overall response. It was calculated from the date of first documentation of response to the date of disease progression or death due to progressive disease.	Yes