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

Sarcoma Alliance for Research through Collaboration

Status and phase

Completed

Phase 2

Conditions

Sarcoma

Treatments

Drug: gemcitabine hydrochloride

Biological: filgrastim

Other: pharmacokinetic study

Biological: pegfilgrastim

Genetic: microarray analysis

Drug: docetaxel

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

Identifiers

NCT00073983

SARC003

Details and patient eligibility

About

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.

Full 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.

Enrollment

54 patients

Sex

All

Ages

4+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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