Neoadjuvant Therapy for Ovarian Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Columbia University
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Jason D. Wright, Columbia University
ClinicalTrials.gov Identifier:
NCT01146795
First received: May 21, 2010
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Epithelial Ovarian Cancer
Primary Peritoneal Cancer
Fallopian Tube Cancer
Drug: Carboplatin, paclitaxel, and bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility of Carboplatin, Paclitaxel and Bevacizumab Neoadjuvant Therapy for Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Event rate of the regimen (neoadjuvant carboplatin, paclitaxel, and bevacizumab) [ Time Frame: Up to 30 days after the last treatment ] [ Designated as safety issue: Yes ]

    Any of the following occurrences will be considered an event:

    • 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 or any event requiring reoperation in chemotherapy cycles after surgery

    The regimen would be considered unfeasible for further study if an event occurs in at least 25% of patients.



Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: After cycles 3, 6, and 9 and three years post-treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: After cycles 3, 6, and 9 and three years post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: May 2010
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab
Three 21 day cycles of carboplatin, paclitaxel, and bevacizumab
Drug: Carboplatin, paclitaxel, and bevacizumab

Carboplatin will be administered at an AUC of 5-6 (at the discretion of the physician) day 1 every 3 weeks, paclitaxel 175 mg/m2 over 3 hours day 1 every 3 weeks and bevacizumab 15 mg/kg day 1 every 3 weeks.

After 3 cycles of chemotherapy patients will be considered for surgical cytoreduction. Patients must fulfill ALL of the following criteria to be considered eligible for surgical exploration. 1) ≥50% reduction in pretreatment 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.


Detailed Description:

This study is designed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have Suspected 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 GOG Performance Status of 0, 1 or 2.
  • Patients with prior anthracycline exposure must have a baseline 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). SGOT (AST), SGPT (ALT), and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE Grade 1).
    • Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade 1.
    • Coagulation function: 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.
  • An approved informed consent and authorization permitting release of personal health information must be signed by the patient or guardian.
  • Eligible patients should be deemed as likely to be medically fit to undergo surgical cytoreduction after 3 cycles of neoadjuvant chemotherapy by a surgical gynecologic oncologist.
  • Patients may receive estrogen +/- progestin replacement.

Exclusion Criteria:

  • 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.
  • 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 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.
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
    • Serious cardiac arrhythmia requiring medication. This does not include atrial fibrillation.
    • CTCAE Grade 3 or greater peripheral vascular disease.
    • History of CVA within six months.
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies including hypersensitivity to any component of bevacizumab
  • Patients with clinically significant proteinuria. Urine protein should be screened by urine protein-creatinine ratio (UPCR). The UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection. Specifically, a UPCR of 1.0 is equivalent to 1.0 grams of protein in a 24 hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send sample to lab with request for urine protein and creatinine levels (separate requests). The lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL). The UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL). Patients must have a UPCR < 1.0 to allow participation in the study.
  • Patients with hypertensive crises or hypertensive encephalopathy
  • History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to day 1.
  • Patients with or with anticipation of a non-study related invasive procedure defined as followed:

    • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab.
    • Major non-study related surgical procedure anticipated during the course of the study.
    • Core biopsy within 7 days prior to first date of bevacizumab.
  • Patients with a GOG Performance Status of Grade 3 or 4 are not eligible.
  • Patients who are pregnant or nursing. Subjects of child-bearing age have to use effective means of contraception.
  • Patients under the age of 18.
  • Patients who have received prior therapy with any anti-VEGF drug, including bevacizumab.
  • Patients with human immunodeficiency virus (HIV).
  • Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should consult the Study Chair.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01146795

Contacts
Contact: Jason Wright, MD 212-305-3410
Contact: Reena M Vattakalam 212-342-6895

Locations
United States, Connecticut
Yale University Not yet recruiting
New Haven, Connecticut, United States, 06510
Contact: Peter Schwartz, MD    203-785-4014      
Principal Investigator: Peter Schwartz, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Jason D Wright, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Robert A Burger, MD    215-728-3150      
Principal Investigator: Lainie Martin, MD         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Susan Modesitt, MD    434-924-5197      
Principal Investigator: Susan Modesitt, MD         
Sponsors and Collaborators
Jason D. Wright
Genentech
Investigators
Principal Investigator: Jason D Wright, MD Columbia University
  More Information

No publications provided

Responsible Party: Jason D. Wright, Levine Family Assistant Professor of Women's Health in Obstetrics and Gynecology, Columbia University
ClinicalTrials.gov Identifier: NCT01146795     History of Changes
Other Study ID Numbers: AAAD8429
Study First Received: May 21, 2010
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Neoplasms by Histologic Type
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014