Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00887809
First received: April 23, 2009
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Sarcoma
Leiomyosarcoma
Malignant Fibrous
Histiocytoma
Angiosarcoma
Drug: gemcitabine and docetaxel with bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial Of Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • is to determine the 6 month progression free rate for sarcoma patients treated with bevacizumab combined with gemcitabine and docetaxel. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the effect of bevacizumab on RECIST response rate when combined with gemcitabine and docetaxel. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the effect of bevacizumab on response rate by alternative criteria (Choi) when combined with gemcitabine and docetaxel. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the effect of bevacizumab on overall survival when combined with gemcitabine and docetaxel. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the toxicity of bevacizumab, gemcitabine and docetaxel [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: April 2009
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 chemotherapy
gemcitabine and docetaxel with bevacizumab
Drug: gemcitabine and docetaxel with bevacizumab
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00887809

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
Investigators
Principal Investigator: William Tap, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00887809     History of Changes
Other Study ID Numbers: 09-015
Study First Received: April 23, 2009
Last Updated: January 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Bevacizumab (avastin)
Gemcitabine
Taxotere (docetaxel)
09-015
Soft tissue

Additional relevant MeSH terms:
Histiocytoma
Hemangiosarcoma
Leiomyosarcoma
Sarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Neoplasms, Muscle Tissue
Gemcitabine
Docetaxel
Bevacizumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on July 26, 2014