search
Back to results

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

Primary Purpose

Ovarian Cancer, Primary PERITONEUM, Fallopian Tube Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel,Cisplatin, Bevacizumab
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring ovary, BEVACIZUMAB, CISPLATIN, TAXOL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Paclitaxel, Cisplatin, Bevacizumab

Outcomes

Primary Outcome Measures

Overall Objective Response
as determined by the GOG RECIST criteria

Secondary Outcome Measures

Full Information

First Posted
December 22, 2007
Last Updated
December 15, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT00588237
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc.

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Primary PERITONEUM, Fallopian Tube Cancer
Keywords
ovary, BEVACIZUMAB, CISPLATIN, TAXOL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Paclitaxel, Cisplatin, Bevacizumab
Intervention Type
Drug
Intervention Name(s)
Paclitaxel,Cisplatin, Bevacizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Objective Response
Description
as determined by the GOG RECIST criteria
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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: Stage not greater than IB. Less than 3 mm invasion without vascular or lymphatic invasion 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: Uncontrolled hypertension, defined as systolic >150 mm Hg or diastolic > 90 mm Hg Myocardial infarction or unstable angina < 6 months prior to registration New York Heart Association (NYHA) Grade II or greater congestive heart failure Serious cardiac arrhythmia requiring medication 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Konner, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org
Description
Memorial Sloan-Kettering Cancer Center

Learn more about this trial

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

We'll reach out to this number within 24 hrs