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Intravenous and Intraperitoneal Paclitaxel, Intraperitoneal Cisplatin, and Intravenous Bevacizumab for the Initial Treatment of Optimal Stage II or III Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00588237
First received: December 22, 2007
Last updated: November 13, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to test whether it is safe to treat your cancer with 3 drugs instead of 2 drugs. After surgery, your cancer is typically treated with 2 drugs called cisplatin and paclitaxel (also known as Taxol). Cisplatin is given through a port in your belly, and Taxol is given both through the belly port and through the vein (IV). Large clinical studies have shown that this treatment gives the best results for women with your cancer. This treatment, however, also causes many side effects, especially belly pain, nerve injury, lowering of the immune system, and infection risk. In the study you are being asked to join, the dose of Cisplatin will be lower in order to try to lessen these problems. This study will also test the safety of adding a 3rd drug called bevacizumab (also known as Avastin). This drug has been shown to shrink ovarian, peritoneal, or fallopian tube cancer in some patients who have advanced disease, despite having received prior treatment for their cancer. Therefore, it may also be effective in patients, like you, who have a new diagnosis.

Unfortunately, Avastin can cause some dangerous side effects in women with advanced cancer. For instance, it can cause a hole in the intestines, and can increase the risk of blood clots and strokes. Avastin has not been given at the same time as IP therapy, so it is not known if this is a safe or effective combination. In this study, IV Avastin will be given in addition to IP cisplatin, IP Taxol, and IV Taxol, to patients like you who have not had any chemotherapy before. This study aims to find out what effects, good and/or bad, that this combination of drugs has on your body and on your type of cancer.


Condition Intervention Phase
Ovarian Cancer
Primary PERITONEUM
Fallopian Tube Cancer
Drug: Paclitaxel,Cisplatin, Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intravenous and Intraperitoneal Paclitaxel, Intraperitoneal Cisplatin, and Intravenous Bevacizumab for the Initial Treatment of Optimal Stage II or III Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • evaluate safety & tolerability of delivering 6 cycles of IV/IP paclitaxel, IP cisplatin, & IV bevacizumab (begun in cycle 2 & continued for a maximum of 22 cycles), as upfront tx in women with optimally debulked stage II/III ovarian,primary periton [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the progression-free survival. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: August 2006
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Paclitaxel, Cisplatin, Bevacizumab
Drug: Paclitaxel,Cisplatin, Bevacizumab
IV paclitaxel, followed by IV Bevacizumab on Day 1. Bevacizumab treatment will begin cycle 2, day 1. IP cisplatin will be given on Day 2, and IP Paclitaxel on Day 8. Subjects will receive up to six cycles of therapy, or until disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Subjects must have signed an approved informed consent.
  • Subjects with histologic diagnosis of epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma, Stage II or III, with optimal (≤ or equal to 1 cm residual disease) residual disease following initial surgery. All subjects must have had appropriate surgery for ovarian, primary peritoneal, or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage. Pathology must be verified at Memorial Sloan-Kettering Cancer Center.
  • Subjects with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma N.O.S.
  • Subjects must have a Karnofsky Performance Status (KPS) of ≥ or equal to 70%.
  • Subjects must be entered no more than 12 weeks postoperatively.
  • Bone marrow function:
  • Absolute neutrophil count (ANC) ≥ than or equal to 1,500/µl (equivalent to Common Toxicity Criteria (CTC) Grade 1)
  • Platelets ≥ than or equal to 100,000/µl (CTC Grade 0-1)
  • Renal function: Creatinine ≤ than or equal to 1.5 mg/dl
  • Hepatic function: Bilirubin ≤ than or equal to 1.5 x ULN (CTC Grade 1) AST ≤ than or equal to 2.5 x ULN (CTC Grade 1)
  • Neurologic function:Neuropathy (sensory) ≤ than CTC Grade 1
  • Urine Protein Creatinine: Urine protein creatinine (UPC) ratio must be < than 1.0 gm. If UPC ratio > than or equal to 1, collection of 24-hour urine measurement of urine protein is recommended as part of the patient's medical management off-study. *
  • UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm. UPC ratio is calculated using one of the following formulas:
  • [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL
  • [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
  • 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 gram 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.
  • Blood coagulation parameters:

PT such that international normalized ratio (INR) is < than or equal to 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT < 1.2 times the upper limit of normal.

  • Patients of childbearing potential must have a negative serum pregnancy test prior to study entry and be practicing an effective form of contraception during the study and for at least 6 months after receiving the final treatment of bevacizumab.
  • Patients must have an Intraperitoneal (IP) port in place. If a patient does not have an IP port, she must be willing to undergo surgical placement of one.

Exclusion Criteria:

  • Subjects with a current diagnosis of epithelial ovarian tumor of low malignant potential (borderline carcinomas) are not eligible. Subjects with a prior diagnosis of a low malignant potential tumor that was surgically resected and who subsequently develop invasive adenocarcinoma are eligible, provided that they have not received prior chemotherapy for any ovarian tumor.
  • Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to enrollment, and the subject remains free of recurrent or metastatic disease.
  • Subjects who have received prior chemotherapy for any abdominal or pelvic tumor are excluded. Subjects may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than 3 years prior to enrollment, and that the subject remains free of recurrent or metastatic disease.
  • Patients with synchronous primary endometrial cancer, or a history of primary endometrial cancer, are excluded unless all of the following conditions are met:

    1. Stage not greater than IB.
    2. Less than 3 mm invasion without vascular or lymphatic invasion
    3. No poorly differentiated subtypes, including papillary serous, clear cell or other FIGO grade 3 lesions
  • Patients with suboptimal (> 1 cm) residual disease, as determined by the operative surgeon.
  • Patients who have received any targeted therapy (including but not limited to vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management of their ovarian, peritoneal primary, or fallopian tube cancer.
  • With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy are excluded.
  • Subjects with acute hepatitis.
  • Subjects with active infection that requires parenteral antibiotics.
  • Patients with serious, non-healing wound, ulcer, or bone fracture are not eligible. This includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
  • 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 6 months of the first date of treatment on this study.
  • Patients with clinically significant cardiovascular disease. This includes:

    1. Uncontrolled hypertension, defined as systolic >150 mm Hg or diastolic > 90 mm Hg
    2. Myocardial infarction or unstable angina < 6 months prior to registration
    3. New York Heart Association (NYHA) Grade II or greater congestive heart failure
    4. Serious cardiac arrhythmia requiring medication
    5. CTCAE grade 2 or greater peripheral vascular disease
  • Patients with major surgical procedure, open biopsy, laparoscopy (including intraperitoneal port placement) or significant traumatic injury within 28 days prior to the first date of bevacizumab therapy. Major surgical procedure anticipated during the course of the study. Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of bevacizumab therapy.
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
  • Patients under the age of 18.
  • Patients who are pregnant or nursing.
  • Evidence of extensive intraperitoneal adhesions at the time of surgery, as determined by the operative surgeon.
  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: NCT00588237

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech, Inc.
Investigators
Principal Investigator: Jason Konner, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00588237     History of Changes
Other Study ID Numbers: 06-064
Study First Received: December 22, 2007
Last Updated: November 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
ovary
BEVACIZUMAB
CISPLATIN
TAXOL

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Bevacizumab
Cisplatin
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014