Phase II Study Of Sequential Gemcitabine Followed By Docetaxel For Recurrent Ewing's Sarcoma, Osteosarcoma, Or Unresectable Or Locally Recurrent Chondrosarcoma [SARC Study]
4 Years
N/A
Both
Sarcoma
Trial Information
Phase II Study Of Sequential Gemcitabine Followed By Docetaxel For Recurrent Ewing's Sarcoma, Osteosarcoma, Or Unresectable Or Locally Recurrent Chondrosarcoma [SARC Study]
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective Response Rate
Outcome 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.
Outcome Time Frame:
After 2, 4, 8 and 12 cycles of therapy, each cycle is 21 days
Safety Issue:
No
Principal Investigator
Shreyaskumar R. Patel, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Sarcoma Alliance for Research through Collaboration
Authority:
United States: Institutional Review Board
Study ID:
SARC003
NCT ID:
NCT00073983
Start Date:
October 2006
Completion Date:
December 2010
Related Keywords:
- Sarcoma
- recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
- chondrosarcoma
- recurrent osteosarcoma
- Chondrosarcoma
- Osteosarcoma
- Sarcoma, Ewing's
- Neuroectodermal Tumors, Primitive, Peripheral
- Sarcoma
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