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 Clinical Trial

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00073983
• Other study ID #: SARC003
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2003
• Last updated: February 8, 2012
• Start date: October 2006
• Est. completion date: December 2010

Study information

• Verified date: February 2012
• Source: Sarcoma Alliance for Research through Collaboration
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00070772

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chondrosarcoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Biological:
• filgrastim
filgrastim
• pegfilgrastim
pegfilgrastim

Drug:
• docetaxel
docetaxel
• gemcitabine hydrochloride
gemcitabine hydrochloride

Genetic:
• microarray analysis
microarray analysis

Other:
• laboratory biomarker analysis
laboratory biomarker analysis
• pharmacokinetic study
pharmacokinetic study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sarcoma Alliance for Research through Collaboration

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	After 2, 4, 8 and 12 cycles of therapy, each cycle is 21 days	No
Secondary	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.	post-cycle 2, 4, 8 and 12	No
Secondary	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.	Throughout the study	Yes
Secondary	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.	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.	No