Clinical trial NCT00073983: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
chondrosarcoma
recurrent osteosarcoma
Lead sponsor: Sarcoma Alliance for Research through Collaboration
Sponsor class: OTHER
First posted: 2003-12-11
Enrollment: 54
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: After 2, 4, 8 and 12 cycles of therapy, each cycle is 21 days
Secondary outcomes:
measure: Time to Progression
timeFrame: post-cycle 2, 4, 8 and 12
measure: Toxicity as Assessed by NCI CTCAE v3.0
timeFrame: Throughout the study
measure: Pharmacokinetics of Gemcitabine Alone and Gemcitabine Followed by Docetaxel at Protocol Specified Timeframe in Participants Enrolled on Study
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: Sarcoma Alliance for Research through Collaboration
name: Shreyaskumar R. Patel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sarcoma Alliance for Research through Collaboration
name: Elizabeth Fox, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.