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Avastin +/- Erlotinib Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors

Primary Purpose

Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
erlotinib
paclitaxel
carboplatin
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • 18 years of age and older
  • Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, primary peritoneal carcinoma, or papillary serous mullerian carcinoma
  • Previous attempted surgical debulking
  • Stage III or IV
  • Willing and able to undergo second look laparoscopy
  • Performance status 0-1 by ECOG scale
  • Peripheral neuropathy < grade 2
  • Life expectancy of 6 months or greater

Exclusion Criteria:

  • Patients with clinically significant cardiovascular disease as outlined in the protocol
  • Neutrophil count < 1,500/mm3; platelet count <100,000/m3
  • Alkaline phosphatase or bilirubin > 1.5 x ULN, SGOT > 5 x ULN
  • Calculated creatinine clearance < 50ml/min
  • Prior chemotherapy or radiotherapy for other malignancy except for the treatment for localized breast cancer greater than five years prior to diagnosis
  • No more than one cycle of first line chemotherapy with carboplatin and paclitaxel
  • Inadequate surgical cytoreduction such that interval cytoreductive surgery could materially improve prognosis
  • Concurrent invasive malignancy
  • Evidence of bleeding diathesis or coagulopathy
  • Evidence of tumor involving major blood vessels on any prior CT scans
  • Surgical wound that has failed to close
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of this study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0
  • Serious non-healing wound, ulcer, or bone fracture
  • Prior treatment with an anti-angiogenic agent
  • Any active bleeding
  • Active psychiatric disease or neurologic symptoms requiring treatment
  • Presence of central nervous system brain metastases
  • Proteinuria at screening as demonstrated by criteria in protocol
  • Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent
  • Known hypersensitivity to Cremophor EL or any component of Avastin
  • Active bacterial, viral, or fungal infections
  • Receiving any other investigational agent
  • History of gastrointestinal perforation
  • Prior therapies targeting the epidermal growth factor receptor
  • Symptoms of bowel obstruction
  • Dependence on TPN or IV hydration

Sites / Locations

  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

carboplatin/paclitaxel/bevacizumab then bevacizumab

carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib

carboplatin/paclitaxel/bevacizumab

Arm Description

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.

Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None

Outcomes

Primary Outcome Measures

Consolidation Progression-Free Survival
Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.
Consolidation Treatment-related Toxicity Rate
Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.

Secondary Outcome Measures

Consolidation Objective Response Rate
Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample.

Full Information

First Posted
August 22, 2007
Last Updated
July 26, 2018
Sponsor
Dana-Farber Cancer Institute
Collaborators
Genentech, Inc., Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00520013
Brief Title
Avastin +/- Erlotinib Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors
Official Title
A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Genentech, Inc., Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research study is to evaluate how patients with newly diagnosed advanced ovarian, fallopian tube, primary peritoneal cancer and papillary serous or clear cell mullerian tumors respond to consolidation therapy with Avastin and erlotinib or Avastin alone over 1 year. These drugs have been used in the treatment of other types of cancers and information from those studies suggests that these agents may help to treat the cancers studied here.
Detailed Description
Objectives: Primary To examine the progression free survival (PFS) of Avastin and Erlotinib (AE) or Avastin (A) as consolidation therapy. Secondary To examine the toxicity between the two consolidative regimens AE vs. A. To assess the response rate of CTA. STATISTICAL DESIGN This study uses a randomized selection design. Both consolidation treatment arms are deemed experimental and are compared against a historical control [McGuire WP et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. NEJM 1996: 334:1-6. PMID:7494563]. With 30 patients in a given arm and 6 months of follow-up, there was 80% power to detect a 61.5% increase in median PFS from 13 months to 21 months assuming 1-sided 10% significance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Papillary Serous Mullerian Tumor, Clear Cell Mullerian Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
carboplatin/paclitaxel/bevacizumab then bevacizumab
Arm Type
Experimental
Arm Description
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (A): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 1 year.
Arm Title
carboplatin/paclitaxel/bevacizumab then bevacizumab/erlotinib
Arm Type
Experimental
Arm Description
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation (AE): Patients received bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle and oral erlotinib 150mg daily for 1 year.
Arm Title
carboplatin/paclitaxel/bevacizumab
Arm Type
Experimental
Arm Description
Induction (CTA): Patients received carboplatin IV AUC 5, paclitaxel IV 175 mg/m2 and bevacizumab IV 15 mg/kg on day 1 (+/- 3d) of a 21 day cycle for 6 cycles. Bevacizumab started with cycle 2. Patients with disease progression based on radiographic evaluation after induction could not advance to the randomized consolidation phase. Consolidation: None
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Avastin, rhuMAB VEGF
Intervention Type
Drug
Intervention Name(s)
erlotinib
Other Intervention Name(s)
Tarceeva
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Taxol
Intervention Type
Drug
Intervention Name(s)
carboplatin
Other Intervention Name(s)
Paraplatin
Primary Outcome Measure Information:
Title
Consolidation Progression-Free Survival
Description
Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation.
Time Frame
Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.
Title
Consolidation Treatment-related Toxicity Rate
Description
Consolidation treatment-related toxicity rates based on CTCAEv3 were defined as rates of maximum grade 3 or higher toxicity events with attribution possible, probable or definite occurring during consolidation treatment and up to 30 days post-treatment.
Time Frame
Assessed every cycle during consolidation treatment and up to 30 days post-treatment. Per protocol, consolidation treatment was a fixed duration of 1 year.
Secondary Outcome Measure Information:
Title
Consolidation Objective Response Rate
Description
Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample.
Time Frame
Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 years of age and older Histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, primary peritoneal carcinoma, or papillary serous mullerian carcinoma Previous attempted surgical debulking Stage III or IV Willing and able to undergo second look laparoscopy Performance status 0-1 by ECOG scale Peripheral neuropathy < grade 2 Life expectancy of 6 months or greater Exclusion Criteria: Patients with clinically significant cardiovascular disease as outlined in the protocol Neutrophil count < 1,500/mm3; platelet count <100,000/m3 Alkaline phosphatase or bilirubin > 1.5 x ULN, SGOT > 5 x ULN Calculated creatinine clearance < 50ml/min Prior chemotherapy or radiotherapy for other malignancy except for the treatment for localized breast cancer greater than five years prior to diagnosis No more than one cycle of first line chemotherapy with carboplatin and paclitaxel Inadequate surgical cytoreduction such that interval cytoreductive surgery could materially improve prognosis Concurrent invasive malignancy Evidence of bleeding diathesis or coagulopathy Evidence of tumor involving major blood vessels on any prior CT scans Surgical wound that has failed to close Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of this study Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0 Serious non-healing wound, ulcer, or bone fracture Prior treatment with an anti-angiogenic agent Any active bleeding Active psychiatric disease or neurologic symptoms requiring treatment Presence of central nervous system brain metastases Proteinuria at screening as demonstrated by criteria in protocol Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent Known hypersensitivity to Cremophor EL or any component of Avastin Active bacterial, viral, or fungal infections Receiving any other investigational agent History of gastrointestinal perforation Prior therapies targeting the epidermal growth factor receptor Symptoms of bowel obstruction Dependence on TPN or IV hydration
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susana Campos, MD, MPH
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Avastin +/- Erlotinib Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Advanced Ovarian, Fallopian Tube, Primary Peritoneal Cancer & Papillary Serous or Clear Cell Mullerian Tumors

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