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Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes

Primary Purpose

Sarcoma, Leiomyosarcoma, Malignant Fibrous

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
gemcitabine
docetaxel
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 Sarcoma focused on measuring Bevacizumab (avastin), Gemcitabine, Taxotere (docetaxel), 09-015, Soft tissue

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed unresectable metastatic or locally recurrent leiomyosarcoma, Malignant Fibrous Histiocytoma (MFH, also known as high grade Undifferentiated Pleomorphic Sarcoma) pleomorphic liposarcoma, rhabdomyosarcoma or angiosarcoma.
  • Zero to one prior chemotherapy regimens for metastatic disease. Prior adjuvant therapy will not count provided it was more than one year previously.
  • Measurable disease as defined by RECIST
  • Adequate performance status - ECOG 0 or 1
  • Patients must be recovered from the toxic effects of prior chemotherapy or radiation. Therapy may not start until at least 3 weeks since prior cytotoxic chemotherapy, two weeks from completion of radiation therapy, and one week for patients on tyrosine kinase inhibitors or other targeted therapy.
  • Age 18 To 75. As it is quite difficult to administer high dose docetaxel with gemcitabine, to the elderly, in order to protect patient safety, we will restrict eligibility to patients between the ages of 18 and 75.
  • Adequate hematologic, hepatic and renal function as defined below
  • Hemoglobin > or = to 8.0 g/dl
  • Absolute neutrophil count > or = to 1,500/mm3
  • Platelet count > or = to 100,000/mm3
  • Total Bilirubin < or = to1.5 x upper limit of normal (ULN).
  • ALT (SGOT) or AST (SGPT) < or = to 5 x ULN.
  • Alkaline Phosphatase < or = to 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases.
  • Serum creatinine 2.0 mg/dL
  • Ability to understand informed consent and comply with treatment protocol
  • Normal cardiac ejection fraction
  • Urine protein:creatinine (UPC) ratio < than or = to 1.0 at screening

Exclusion Criteria:

  • Uncontrolled intercurrent illness including infection or congestive heart failure within 6 months.
  • Prior therapy with gemcitabine, docetaxel or bevacizumab
  • Patients receiving other investigational agents
  • Patients with known brain metastases
  • Pregnancy or unwillingness to use effective birth control
  • Patients with HIV disease will be permitted, only if they are on effective anti-retroviral therapy, have a CD4 count greater than 400, and have had no opportunistic infections within the past 6 months.
  • Patients on anti-coagulation will be permitted if they are on a stable dose of warfarin or low-molecular weight heparin, and have had no major bleeds within the past 6 months.
  • Inability to comply with study and/or follow-up procedures.
  • Life expectancy of less than 12 weeks.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
  • Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last three years
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg lasting > 24 hours on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection), requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
  • Symptomatic peripheral vascular disease
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Serious, non-healing wound, active ulcer, or non-healing bone fracture
  • Proteinuria at screening as demonstrated by
  • Urine protein:creatinine (UPC) ratio > or = to 1.0 at screening (patients discovered to have UPC ratio > or = to 1.0 at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • Known hypersensitivity to any component of bevacizumab
  • Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
  • History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3 months prior to study enrollment.
  • Any history of stroke or transient ischemic attack within 6 months
  • History of myocardial infarction or unstable angina within 6 months

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

gemcitabine and docetaxel with bevacizumab

Arm Description

Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.

Outcomes

Primary Outcome Measures

Overall Objective Response
Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Secondary Outcome Measures

Full Information

First Posted
April 23, 2009
Last Updated
December 21, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00887809
Brief Title
Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
Official Title
Phase II Trial Of Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
October 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

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to test whether an experimental drug called bevacizumab given together with gemcitabine and docetaxel, a standard chemotherapy regimen for sarcoma, can help sarcoma patients. This trial will examine what effects, good and/or bad the combination of gemcitabine, docetaxel and bevacizumab has on sarcoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Leiomyosarcoma, Malignant Fibrous, Histiocytoma, Angiosarcoma
Keywords
Bevacizumab (avastin), Gemcitabine, Taxotere (docetaxel), 09-015, Soft tissue

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
gemcitabine and docetaxel with bevacizumab
Arm Type
Experimental
Arm Description
Patients will receive bevacizumab at 15 mg/kg on day 1 of each 21-day cycle intravenously over 30 minutes followed by a one hour (+30/-15 min) break. For cycles 1 through 6, gemcitabine will be administered at 900 mg/m2 over 90 minutes on day 1 and 8 of a 21-day cycle. Docetaxel will be administered at 75 mg/m2, over 60 minutes, on day 8. This will be followed by either 5 days of filgrastim or a single injection of pegfilgrastim. For cycles 7 and beyond, gemcitabine will be given at 800 mg/m2 over 30 minutes on day 1 and 8; docetaxel will be given at 35 mg/m2 over 30 minutes, also on days 1 and 8.
Intervention Type
Drug
Intervention Name(s)
gemcitabine
Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Primary Outcome Measure Information:
Title
Overall Objective Response
Description
Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed unresectable metastatic or locally recurrent leiomyosarcoma, Malignant Fibrous Histiocytoma (MFH, also known as high grade Undifferentiated Pleomorphic Sarcoma) pleomorphic liposarcoma, rhabdomyosarcoma or angiosarcoma. Zero to one prior chemotherapy regimens for metastatic disease. Prior adjuvant therapy will not count provided it was more than one year previously. Measurable disease as defined by RECIST Adequate performance status - ECOG 0 or 1 Patients must be recovered from the toxic effects of prior chemotherapy or radiation. Therapy may not start until at least 3 weeks since prior cytotoxic chemotherapy, two weeks from completion of radiation therapy, and one week for patients on tyrosine kinase inhibitors or other targeted therapy. Age 18 To 75. As it is quite difficult to administer high dose docetaxel with gemcitabine, to the elderly, in order to protect patient safety, we will restrict eligibility to patients between the ages of 18 and 75. Adequate hematologic, hepatic and renal function as defined below Hemoglobin > or = to 8.0 g/dl Absolute neutrophil count > or = to 1,500/mm3 Platelet count > or = to 100,000/mm3 Total Bilirubin < or = to1.5 x upper limit of normal (ULN). ALT (SGOT) or AST (SGPT) < or = to 5 x ULN. Alkaline Phosphatase < or = to 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases. Serum creatinine 2.0 mg/dL Ability to understand informed consent and comply with treatment protocol Normal cardiac ejection fraction Urine protein:creatinine (UPC) ratio < than or = to 1.0 at screening Exclusion Criteria: Uncontrolled intercurrent illness including infection or congestive heart failure within 6 months. Prior therapy with gemcitabine, docetaxel or bevacizumab Patients receiving other investigational agents Patients with known brain metastases Pregnancy or unwillingness to use effective birth control Patients with HIV disease will be permitted, only if they are on effective anti-retroviral therapy, have a CD4 count greater than 400, and have had no opportunistic infections within the past 6 months. Patients on anti-coagulation will be permitted if they are on a stable dose of warfarin or low-molecular weight heparin, and have had no major bleeds within the past 6 months. Inability to comply with study and/or follow-up procedures. Life expectancy of less than 12 weeks. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last three years Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg lasting > 24 hours on antihypertensive medications) Any prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association (NYHA) Grade II or greater congestive heart failure Significant vascular disease (e.g., aortic aneurysm, aortic dissection), requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 Symptomatic peripheral vascular disease Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment Serious, non-healing wound, active ulcer, or non-healing bone fracture Proteinuria at screening as demonstrated by Urine protein:creatinine (UPC) ratio > or = to 1.0 at screening (patients discovered to have UPC ratio > or = to 1.0 at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). Known hypersensitivity to any component of bevacizumab Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential History of hemoptysis (bright red blood of 1/2 teaspoon or more per episode) within 3 months prior to study enrollment. Any history of stroke or transient ischemic attack within 6 months History of myocardial infarction or unstable angina within 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Tap, 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

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Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes

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