Neoadjuvant Therapy for Ovarian Cancer
Condition: Epithelial Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms
Intervention: Carboplatin; Paclitaxel; Bevacizumab
Intervention description: 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.; Paclitaxel 175 mg/m2 over 3 hours day 1 every 3 weeks in combination with Carboplatin and Bevacizumab.; Bevacizumab 15 mg/kg day 1 every 3 weeks in combination with Paclitaxel and Carboplatin.
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

          -  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. 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.

               -  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 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. Vascular endothelial growth factor (VEGF)

          -  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.