Neoadjuvant Chemotherapy IV Carboplatin With Weekly Paclitaxel \Bevacizumab for Primary Ovarian

Phase I Evaluation of Intravenous Carboplatin With Weekly Paclitaxel and Bevacizumab in Patients Undergoing Neoadjuvant Chemotherapy for Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

The purpose of this study is to determine the maximum tolerated dose (MTD) of intravenous weekly paclitaxel given with intravenous carboplatin and bevacizumab in patients with epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that are to receive neoadjuvant chemotherapy (prior to surgical cytoreduction). Patients will then undergo surgery which will allow an objective measure of response to the above regimen as well as assessment of surgical outcomes.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: Bevacizumab; Drug: Paclitaxel

Detailed Description

Phase I study proposed to evaluate:

• Tolerability of IV regimen carboplatin, paclitaxel and bevacizumab in the neoadjuvant setting prior to surgery.
• Safety/Toxicity of IV regimen in this patient population
• Treatment is Carboplatin area under the concentration curve (AUC) 5, Bevacizumab 15mg/m2, and starting dose of paclitaxel of 60mg/m2 and will be escalated in intervals of 10mg/m2 to a maximum dose of 80mg/m2.
• Patients will receive cycles 1-3 of carboplatin, bevacizumab, and paclitaxel and then cycle 4 will be carboplatin and paclitaxel followed by surgical intervention within 6 weeks of cycle 4.
• Post surgical treatment per physician discretion

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• histology,cytologically diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer
• FIGO (International Federation of Gynecology and Obstetrics stage III or IV disease
• GOG (Gynecologic Oncology Group) Performance Status 0,1,2
• No prior surgery for their malignancy
• Adequate bone marrow function
• Platelet count greater than or equal to 100,000
• Renal Function: Creatinine < 1.5 institutional upper limit normal
• Hepatic Function: Bilirubin less than 1.5 ULN (upper limit of normal)
• Hepatic Function: SGOT (serum glutamate oxaloacetate transaminase) and Alkaline Phosphate
• Neurologic Function: Neuropathy less than CTCAE (Common Toxicity Criteria for Adverse Effects)grade 1
• Coagulation Functions: INR<1.5 and PTT ,1.2 times the upper limit of normal
• Measurable disease

Exclusion Criteria:

• Previous cancer related surgery
• Received prior chemotherapy, immunotherapy, radiotherapy, hormonal therapy or biologic therapy for their ovarian, fallopian tube or primary peritoneal cancer.
• Borderline ovarian tumors, recurrent epithelial ovarian or primary peritoneal cancer or non-epithelial ovarian are not eligible.
• Other cancers within 5 years (other than non-melanoma skin cancer)
• Acute Hepatitis or end stage liver disease
• History of prior gastrointestinal perforation
• Evidence of abdominal free air not explained by paracentesis
• Sign or symptoms of gastrointestinal obstruction
• Active bleeding or pathologic conditions that carry high risk of bleeding
• CNS (Central Nervous System) disease
• Clinically Significant cardiovascular disease
• Known hypersensitivity to Chinese Hamster ovary cell products or other recombinant human or humanized antibodies
• Clinically significant proteinuria.
• Hypertensive crises or hypertensive encephalopathy
• History of hemoptysis
• Any non-study related invasive procedure within 28 days fo first date of bevacizumab
• GOG performance status 3 or 4
• Patients who are pregnant or nursing.
• Under the age of 18
• Received prior treatment of bevacizumab or any anti-VEGF (vascular endothelial growth factor) drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carboplatin; AUC 5.0 or 6.0	Drug: carboplatin; Carboplatin AUC 5.0 or 6.0 will be administered on day 1 during cycle 1-3. Treatment cycle consists of 21 days duration.; Other Names: CBDCA; Paraplatin®
Experimental: Bevacizumab; 15 mg/kg	Drug: Bevacizumab; Bevacizumab 15 mg/kg administered on Day 1 during cycle 1-3. Treatment cycle consists of 21 days duration.; Other Names: Avastin
Experimental: Paclitaxel; 60-80 mg/m2	Drug: Paclitaxel; 60-80 mg/m2 administered on Day 1, 8 & 15 during cycle 1-3. Treatment cycle consists of 21 days duration.; Other Names: Taxol; Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerated Dose	To determine the maximum tolerated dose of carboplatin AUC5 administered Day 1 Cycles 1-4, weekly paclitaxel 60-80mg/m2 administered on Day 1, 8,and 15 for 3 weeks cycles 1-4, bevacizumab 15mg/kg administered Day 1 Cycles 1-3 prior to surgical intervention.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity and Response Rates Based on Imaging and Surgical Outcomes	Determine the safety/toxicity of this regimen in this patient population. Estimate the percent of patients undergoing successful cytoreductive surgery to optimal disease (<1 cm greatest tumor diameter) following neoadjuvant chemotherapy with carboplatin, paclitaxel and bevacizumab in patients with epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. Assess the 30 day morbidity and mortality following surgical intervention. To describe the response rate for patients treated with neoadjuvant carboplatin, weekly paclitaxel, and bevacizumab using RECIST and GCIG response criteria prior to surgical intervention. Response was determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 6 months

Collaborators and Investigators

• Sponsor: Ritu Salani
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Ritu Salani, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Jamesline

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: October 11, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Actual): February 8, 2018
• Last Update Submitted That Met QC Criteria: February 7, 2018
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: cancer; bevacizumab; paclitaxel; carboplatin; ovarian; fallopian tube; primary peritoneal
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Adnexal Diseases; Fallopian Tube Diseases; Fallopian Tube Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Carboplatin; Paclitaxel; Bevacizumab
• Other Study ID Numbers: OSU-09149; NCI-2012-00512 (Registry Identifier: Clinical Trials Reporting Program (CTRP))