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Gemcitabine and Docetaxel in Treating Patients With Recurrent Osteosarcoma (Closed to Accrual as of 12/21/06) or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma

Primary Purpose

Sarcoma

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
filgrastim
pegfilgrastim
docetaxel
gemcitabine hydrochloride
microarray analysis
laboratory biomarker analysis
pharmacokinetic study
Sponsored by
Sarcoma Alliance for Research through Collaboration
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, chondrosarcoma, recurrent osteosarcoma

Eligibility Criteria

4 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed* diagnosis of 1 of the following: Recurrent high-grade osteosarcoma (closed to accrual as of 12/21/06) or Ewing's sarcoma Progressive disease after standard therapy Received no more than 2 additional salvage regimens Chondrosarcoma Unresectable OR locally recurrent and unable to be completely resected NOTE: *Biopsy required for isolated pulmonary recurrences Measurable disease At least 1 unidimensionally measurable lesion by medical imaging techniques Ascites, pleural effusions, and bone marrow disease are not considered measurable disease PATIENT CHARACTERISTICS: Age 4 and over Performance status ECOG (Eastern Cooperative Oncology Group) 0-2 (≥ 18 years of age) Karnofsky 50-100% (11-17 years of age) Lansky 50-100% (≤ 10 years of age) Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 8.0 g/dL (transfusion allowed) Hepatic Bilirubin ≤ upper limit of normal (ULN) (except for patients with Gilbert's syndrome) ALT ≤ 2.5 times ULN Renal Creatinine clearance or radioisotope glomerular filtration rate > 70 mL/min/1.73 m^2 OR Serum creatinine ≤ ULN for age: Ages 5 and under ≤ 0.8 mg/dL Ages 6 to 10 ≤ 1.0 mg/dL Ages 11 to 15 ≤ 1.2 mg/dL Ages 16 to 18 ≤ 1.5 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation Sensory or motor neuropathy due to prior chemotherapy ≤ grade 1 Sensory or motor neuropathy due to prior surgery or tumor involvement ≤ grade 2 AND stable or improving No active or uncontrolled infection No known hypersensitivity reaction to docetaxel or other polysorbate 80-formulated agents PRIOR CONCURRENT THERAPY: Biologic therapy At least 72 hours since prior filgrastim (G-CSF) No prior allogeneic transplantation No concurrent immunotherapy Chemotherapy At least 2 weeks since prior myelosuppressive therapy At least 6 months since prior myeloablative therapy No prior gemcitabine No prior taxanes No other concurrent chemotherapy Endocrine therapy Concurrent hormonal therapy allowed Radiotherapy At least 6 weeks since prior local radiotherapy At least 4 months since prior extensive radiotherapy to more than 50% of the pelvis At least 4 months since prior cranial spinal radiotherapy At least 6 months since prior total body irradiation No concurrent radiotherapy Surgery No concurrent surgery Other Recovered from all prior therapy No other concurrent investigational anticancer therapy

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Objective Response Rate
    Patients will be evaluated up to 4 time points(after 2,4,8 and 12 cycles of therapy), each cycle is 21 days. Per RECIST 1.0 and assessed by CT/MRI disease status will be categorized as R=CR/PR(response), F=progressive disease or death(failure), or S(stable disease=neither R nor F) based on the change from baseline. A patient with outcome R or F at any stage is scored as having that overall outcome, a patient with outcome S is re-evaluated after subsequent cycles of therapy. Patients who receive more than 14 cycles of therapy will be scored as the outcome at completion of cycle 14.

    Secondary Outcome Measures

    Time to Progression
    Stable disease is measured from the start of the treatment until the criteria for disease progression are met, taking as reference the smallest measurements recorded since the treatment started. The clinical relevance of the duration of stable disease varies for different tumor types and grades. Bayesian statistical model is used. Timepoints for evaluation are post-cycle 2, 4, 8 and 12 using RECIST 1.0 criteria.
    Toxicity as Assessed by NCI CTCAE v3.0
    Toxicity was graded according to Common Terminology Criteria for Adverse Events v.3.0 (CTCAE v.3.0). For gemcitabine or docetaxel related grade 3 or 4 non-hematological toxicities or hematological toxicities (grade 3 or 4 neutropenia for ≥ 7 days, grade 4 thrombocytopenia, or any platelet transfusion), both agents were withheld until the toxicity was ≤ grade 1. If the toxicity recovered to ≤ grade 1 by cycle day 35, the dose of both agents was reduced for all subsequent cycles. If the toxicity did not resolve by day 35, protocol therapy was discontinued.
    Pharmacokinetics of Gemcitabine Alone and Gemcitabine Followed by Docetaxel at Protocol Specified Timeframe in Participants Enrolled on Study
    Blood samples for the determination of gemcitabine (and its metabolite dFdU) will be obtained prior to infusion, at 75 and 85 minutes (steady state), and 95 105 and 120 minutes, after the start of the 90 minute infusion on day 1 and day 8 of cycle 1. On day 8, docetaxel pharmacokinetics will be performed prior to infusion, 55 minutes (5 minutes prior to the end of infusion), 30 minutes post infusion, 5 hr and 24hr post infusion.

    Full Information

    First Posted
    December 10, 2003
    Last Updated
    February 8, 2012
    Sponsor
    Sarcoma Alliance for Research through Collaboration
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00073983
    Brief Title
    Gemcitabine and Docetaxel in Treating Patients With Recurrent Osteosarcoma (Closed to Accrual as of 12/21/06) or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma
    Official Title
    Phase II Study Of Sequential Gemcitabine Followed By Docetaxel For Recurrent Ewing's Sarcoma, Osteosarcoma, Or Unresectable Or Locally Recurrent Chondrosarcoma [SARC Study]
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2006 (undefined)
    Primary Completion Date
    January 2010 (Actual)
    Study Completion Date
    December 2010 (Actual)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Sarcoma Alliance for Research through Collaboration

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    RATIONALE: Drugs used in chemotherapy, such as gemcitabine and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gemcitabine with docetaxel may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with docetaxel in treating patients who have recurrent osteosarcoma, recurrent Ewing's sarcoma, or unresectable or locally recurrent chondrosarcoma.
    Detailed Description
    OBJECTIVES: Primary Determine the objective response rate in patients with recurrent osteosarcoma or Ewing's sarcoma or unresectable or locally recurrent chondrosarcoma treated with sequential gemcitabine and docetaxel. Secondary Determine the time to progression in patients treated with this regimen. Assess the toxicity of this regimen in these patients. Compare the pharmacokinetics of this regimen vs gemcitabine alone in these patients. Obtain tumor samples for cDNA microarray analysis of gene expression and development of cell lines and xenotransplantation models. OUTLINE: This is a nonrandomized, multicenter study. Patients are stratified according to diagnosis recurrent osteosarcoma vs recurrent Ewing's sarcoma vs unresectable or locally recurrent chondrosarcoma). Patients receive gemcitabine intravenously over 90 minutes on days 1 and 8 and docetaxel intravenously over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover. Patients may receive pegfilgrastim SC on day 9 (once per course) as an alternative to G-CSF. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Optional blood samples are collected at baseline and periodically during study for pharmacokinetics studies. Optional tumor tissue samples from biopsy or surgical resection are analysed for cDNA microarray analysis of gene expression. Patients are followed every 3 months for 1 year and then every 6 months for 1 year. PROJECTED ACCRUAL: A maximum of 120 patients (40 per stratum) will be accrued for this study within 17-24 months.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sarcoma
    Keywords
    recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, chondrosarcoma, recurrent osteosarcoma

    7. Study Design

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

    8. Arms, Groups, and Interventions

    Intervention Type
    Biological
    Intervention Name(s)
    filgrastim
    Intervention Description
    filgrastim
    Intervention Type
    Biological
    Intervention Name(s)
    pegfilgrastim
    Intervention Description
    pegfilgrastim
    Intervention Type
    Drug
    Intervention Name(s)
    docetaxel
    Intervention Description
    docetaxel
    Intervention Type
    Drug
    Intervention Name(s)
    gemcitabine hydrochloride
    Intervention Description
    gemcitabine hydrochloride
    Intervention Type
    Genetic
    Intervention Name(s)
    microarray analysis
    Intervention Description
    microarray analysis
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Intervention Description
    laboratory biomarker analysis
    Intervention Type
    Other
    Intervention Name(s)
    pharmacokinetic study
    Intervention Description
    pharmacokinetic study
    Primary Outcome Measure Information:
    Title
    Objective Response Rate
    Description
    Patients will be evaluated up to 4 time points(after 2,4,8 and 12 cycles of therapy), each cycle is 21 days. Per RECIST 1.0 and assessed by CT/MRI disease status will be categorized as R=CR/PR(response), F=progressive disease or death(failure), or S(stable disease=neither R nor F) based on the change from baseline. A patient with outcome R or F at any stage is scored as having that overall outcome, a patient with outcome S is re-evaluated after subsequent cycles of therapy. Patients who receive more than 14 cycles of therapy will be scored as the outcome at completion of cycle 14.
    Time Frame
    After 2, 4, 8 and 12 cycles of therapy, each cycle is 21 days
    Secondary Outcome Measure Information:
    Title
    Time to Progression
    Description
    Stable disease is measured from the start of the treatment until the criteria for disease progression are met, taking as reference the smallest measurements recorded since the treatment started. The clinical relevance of the duration of stable disease varies for different tumor types and grades. Bayesian statistical model is used. Timepoints for evaluation are post-cycle 2, 4, 8 and 12 using RECIST 1.0 criteria.
    Time Frame
    post-cycle 2, 4, 8 and 12
    Title
    Toxicity as Assessed by NCI CTCAE v3.0
    Description
    Toxicity was graded according to Common Terminology Criteria for Adverse Events v.3.0 (CTCAE v.3.0). For gemcitabine or docetaxel related grade 3 or 4 non-hematological toxicities or hematological toxicities (grade 3 or 4 neutropenia for ≥ 7 days, grade 4 thrombocytopenia, or any platelet transfusion), both agents were withheld until the toxicity was ≤ grade 1. If the toxicity recovered to ≤ grade 1 by cycle day 35, the dose of both agents was reduced for all subsequent cycles. If the toxicity did not resolve by day 35, protocol therapy was discontinued.
    Time Frame
    Throughout the study
    Title
    Pharmacokinetics of Gemcitabine Alone and Gemcitabine Followed by Docetaxel at Protocol Specified Timeframe in Participants Enrolled on Study
    Description
    Blood samples for the determination of gemcitabine (and its metabolite dFdU) will be obtained prior to infusion, at 75 and 85 minutes (steady state), and 95 105 and 120 minutes, after the start of the 90 minute infusion on day 1 and day 8 of cycle 1. On day 8, docetaxel pharmacokinetics will be performed prior to infusion, 55 minutes (5 minutes prior to the end of infusion), 30 minutes post infusion, 5 hr and 24hr post infusion.
    Time Frame
    Gemcitibine: 0hr, 75, 85, 95, 105 and 120 min after the start of the 90 minute infusion; docetaxel: 0hr, 55 min, 30 min post infusion, 5hr and 24hr post infusion.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    4 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Histologically confirmed* diagnosis of 1 of the following: Recurrent high-grade osteosarcoma (closed to accrual as of 12/21/06) or Ewing's sarcoma Progressive disease after standard therapy Received no more than 2 additional salvage regimens Chondrosarcoma Unresectable OR locally recurrent and unable to be completely resected NOTE: *Biopsy required for isolated pulmonary recurrences Measurable disease At least 1 unidimensionally measurable lesion by medical imaging techniques Ascites, pleural effusions, and bone marrow disease are not considered measurable disease PATIENT CHARACTERISTICS: Age 4 and over Performance status ECOG (Eastern Cooperative Oncology Group) 0-2 (≥ 18 years of age) Karnofsky 50-100% (11-17 years of age) Lansky 50-100% (≤ 10 years of age) Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 8.0 g/dL (transfusion allowed) Hepatic Bilirubin ≤ upper limit of normal (ULN) (except for patients with Gilbert's syndrome) ALT ≤ 2.5 times ULN Renal Creatinine clearance or radioisotope glomerular filtration rate > 70 mL/min/1.73 m^2 OR Serum creatinine ≤ ULN for age: Ages 5 and under ≤ 0.8 mg/dL Ages 6 to 10 ≤ 1.0 mg/dL Ages 11 to 15 ≤ 1.2 mg/dL Ages 16 to 18 ≤ 1.5 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation Sensory or motor neuropathy due to prior chemotherapy ≤ grade 1 Sensory or motor neuropathy due to prior surgery or tumor involvement ≤ grade 2 AND stable or improving No active or uncontrolled infection No known hypersensitivity reaction to docetaxel or other polysorbate 80-formulated agents PRIOR CONCURRENT THERAPY: Biologic therapy At least 72 hours since prior filgrastim (G-CSF) No prior allogeneic transplantation No concurrent immunotherapy Chemotherapy At least 2 weeks since prior myelosuppressive therapy At least 6 months since prior myeloablative therapy No prior gemcitabine No prior taxanes No other concurrent chemotherapy Endocrine therapy Concurrent hormonal therapy allowed Radiotherapy At least 6 weeks since prior local radiotherapy At least 4 months since prior extensive radiotherapy to more than 50% of the pelvis At least 4 months since prior cranial spinal radiotherapy At least 6 months since prior total body irradiation No concurrent radiotherapy Surgery No concurrent surgery Other Recovered from all prior therapy No other concurrent investigational anticancer therapy
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Shreyaskumar R. Patel, MD
    Organizational Affiliation
    Sarcoma Alliance for Research through Collaboration
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Elizabeth Fox, MD
    Organizational Affiliation
    Sarcoma Alliance for Research through Collaboration
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    Citation
    Kilgour-Christie J, Czarnecki A: Pulmonary adverse drug reactions in patients treated with gemcitabine and a combination of gemcitabine and a taxane. [Abstract] J Clin Oncol 23 (Suppl 16): A-8274, 796s, 2005.
    Results Reference
    background
    PubMed Identifier
    22363068
    Citation
    Fox E, Patel S, Wathen JK, Schuetze S, Chawla S, Harmon D, Reinke D, Chugh R, Benjamin RS, Helman LJ. Phase II study of sequential gemcitabine followed by docetaxel for recurrent Ewing sarcoma, osteosarcoma, or unresectable or locally recurrent chondrosarcoma: results of Sarcoma Alliance for Research Through Collaboration Study 003. Oncologist. 2012;17(3):321. doi: 10.1634/theoncologist.2010-0265. Epub 2012 Feb 23.
    Results Reference
    derived

    Learn more about this trial

    Gemcitabine and Docetaxel in Treating Patients With Recurrent Osteosarcoma (Closed to Accrual as of 12/21/06) or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma

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