Neoadjuvant Therapy for Ovarian Cancer

NCT01146795 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAD8429
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

This study is to determine the feasibility of administering neoadjuvant carboplatin, paclitaxel, and bevacizumab without excessive dose modification or cycle delay in patients with epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer. This study will also investigate the rate of optimal cytoreduction, response rate and progression free and overall survival, and to assess the quality of life for patients with epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer treated with neoadjuvant carboplatin, paclitaxel and bevacizumab.

Conditions

Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Protocol Defined Adverse Events in Patients Receiving Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab

  This is to assess the feasibility of delivering multiple cycles of the study treatment without excessive dose modification or cycle delays. The regimen would be considered unfeasible for further study if there were 5 or more of the following events within the first 15 patients, 7 or more of these events within the first 30 patients, or 8 or more of these events within the first 45 patients: * Delay of day 1 of therapy \> 3 weeks from the expected day 1 of that cycle * Febrile neutropenia requiring hospitalization * Grade 4 thrombocytopenia * Grade 1-5 gastrointestinal perforation * Grade 3-4 hemorrhagic toxicity * Grade 3-4 arterial thromboembolic complications * Grade 4 hypertension * Grade 4 proteinuria * Fascial dehiscence

  Up to 30 days after completion of 9 cycles of treatment and/or early discontinuation (approximately up to 12 months)

Secondary Outcomes (3)

• Response Rate

  Cycle 3, Cycle 6, Cycle 9 and 3 years post-treatment

• Quality of Life (QOL) Score

  Baseline, Cycle 3, Cycle 6, Cycle 9

• Progression-free Survival (PFS)

  Up to 3 years

Study Arms (1)

Carboplatin, Paclitaxel, and Bevacizumab

EXPERIMENTAL

Three 21 day cycles of carboplatin, paclitaxel, and bevacizumab. After 3 cycles of chemotherapy patients will be considered for surgical cytoreduction. Patients must fulfill all criteria to be considered eligible for surgical exploration: 1) ≥50% reduction in pretreatment cancer antigen 125 (CA-125) and 2) No medical contraindications to surgery. After surgical cytoreduction all patients will receive an additional 6 cycles of chemotherapy (cycles 4-9) regardless of disease status at the time of exploration. Chemotherapy should be re-instituted within 6 weeks of the surgical procedure. Bevacizumab will be omitted from cycle 4 of chemotherapy. Patients who do NOT undergo surgical resection should receive cycles 4-9 of therapy. In this instance bevacizumab may be included in cycle 4.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Carboplatin DRUG

Carboplatin will be administered at a concentration-time curve (AUC) of 5-6 (at the discretion of the physician) day 1 every 3 weeks in combination with Paclitaxel and Bevacizumab.

Also known as: Paraplatin

Carboplatin, Paclitaxel, and Bevacizumab

Paclitaxel DRUG

Paclitaxel 175 mg/m2 over 3 hours day 1 every 3 weeks in combination with Carboplatin and Bevacizumab.

Also known as: Taxol

Carboplatin, Paclitaxel, and Bevacizumab

Bevacizumab DRUG

Bevacizumab 15 mg/kg day 1 every 3 weeks in combination with Paclitaxel and Carboplatin.

Also known as: Avastin

Carboplatin, Paclitaxel, and Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have Suspected Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease.
• Cytologic or histologic diagnosis of a carcinoma felt by the investigator to be compatible with epithelial cancer of the ovary, fallopian tube, or primary peritoneum
• Patients must have a Performance Status of 0, 1 or 2.
• Patients with prior anthracycline exposure must have a baseline multigated acquisition scan (MUGA) or echocardiogram prior to study entry.
• Patients must have adequate:
• Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1500/υl, equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade 1. This ANC cannot have been induced or supported by granulocyte colony stimulating factors.
• Platelets greater than or equal to 100,000/υl (CTCAE Grade 0-1).
• Hematocrit \> 21%.
• Renal function: Creatinine \< 1.5 x institutional upper limit of normal (ULN), CTCAE Grade 1.
• Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE Grade 1). AST, ALT, and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE Grade 1). Aspartate transaminase (AST) and alanine transaminase (ALT)
• Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade 1.
• Coagulation function: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) - PT such that international normalized ratio (INR) is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolism) and a PTT \< 1.2 times the upper limit of normal.
• Patients must have measurable disease. Patients may or may not have cancer-related symptoms.
• Baseline CA-125 must be ≥ 70 units/mL.
• Patients must have met all pre-entry requirements.

You may not qualify if:

• Patients should NOT have undergone any prior cancer directed surgery (exploration, debulking, etc), with the exception of a minor procedure such as biopsy or cytology specimen.
• Patients who have received prior chemotherapy, immunotherapy, radiotherapy, hormonal therapy or biologic therapy for their ovarian or primary peritoneal cancer are not eligible.
• Patients with borderline ovarian tumors, recurrent epithelial ovarian or primary peritoneal cancer or non-epithelial ovarian cancer are not eligible.
• Patients with a CA125:CEA ratio \<25. Carcinoembryonic Antigen (CEA)
• Patients with other cancers (other than non-melanoma skin cancer) within the last five years.
• Patients with acute hepatitis or end stage liver disease.
• Patients with serious non-healing wound, ulcer or bone fracture. This includes history of abdominal fistula or intra-abdominal abscess within 6 months. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.
• History of prior gastrointestinal perforation.
• Patients with evidence of abdominal free air not explained by paracentesis.
• Patients with signs or symptoms of gastrointestinal obstruction including those receiving total parenteral nutrition (TPN), intravenous hydration or tube feeds.
• Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels by imaging, regardless of whether any chance of requiring vascular reconstruction.
• Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study. Patients with treated brain metastases can enter the study. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with central nervous system (CNS) metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
• Patients with clinically significant cardiovascular disease. This includes:
• Uncontrolled hypertension, defined as systolic \> 140 mm Hg or diastolic \> 90 mm Hg.
• Myocardial infarction or unstable angina within 6 months of day 1 prior to registration.

Sponsors & Collaborators

• Jason D. Wright: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms

Interventions

Carboplatin; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jason Wright, MD
• Organization: Columbia University

jw2459@cumc.columbia.edu

212-305-3410

Study Officials

• Jason D Wright, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sol Goldman Associate Professor of Gynecology Oncology (in Obstetrics and Gynecology)

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: June 22, 2010
• Study Start: May 17, 2010
• Primary Completion: April 13, 2015
• Study Completion: April 13, 2015
• Last Updated: February 9, 2021
• Results First Posted: February 9, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)