Protocol Number: 04-C-0001

Title:

Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing's Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma

Number:

04-C-0001

Summary:

Background

-Gemcitabine and docetaxel are active antineoplastic agents with a broad spectrum of clinical activity.

-In single agent phase I trials, gemcitabine and docetaxel have shown some activity in patients with Ewing's sarcoma and osteosarcoma. Chondrosarcomas are known to be refractory to standard chemotherapeutic regimens.

-A variety of schedules and doses of gemcitabine in combination with docetaxel have been studied in clinical trials.

-Two clinical trials have reported response rates of approximately 50% when the drugs are given sequentially with gemcitabine followed by docetaxel. In addition, in vitro data supports the synergy of sequential gemcitabine-docetaxel therapy.[3]

Objectives

-The primary objective of this study is to determine the objective response rate of sequential gemcitabine-docetaxel in patients with recurrent Ewing's sarcoma, recurrent osteosarcoma, and unresectable or locally recurrent chondrosarcomas.

-Additionally, the pharmacokinetic of gemcitabine and docetaxel will be studied in this patient population and when available, tumor samples for cDNA microarray analysis of gene expression and development of cell lines and xenotransplantation models will be obtained.

Eligibility

-Subjects greater than or equal to 4 years of age with relapsed or refractory osteosarcoma, or Ewing's sarcoma or unresectable or locally recurrent chondrosarcoma are eligible.

Design

-The study will be conducted with the Sarcoma Alliance for Research through Collaboration (SARC). It is an open lable single stage phase 2 study conducted in 3 cohorts of patients (osteosarcoma, Ewing's sarcoma or chondrosarcoma).

-Gemcitabine (675 mg/m(2)) is administered by intravenous infusion over 90minutes on day 1 and 8; docetaxel (75 mg/m(2)) by intravenous infusion over 1 hour is administered after gemcitabine on day 8. Growth factor support with filgrastim or pegfilgrastim begins on day 9. Each cycle is 21 days.

-The study will be conducted using baysean formulation for each cohort. Threshold interesting response rate are 35% in each of the Ewing's and osteosarcoma subgroups, and 20% in the chondrosarcoma subgroup. Using baysean formulation, if the threshold interesting response rates are not maintained, the trial will be closed. A maximum of 40 patients will be enrolled to each cohort.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

A. Patients with recurrent high grade osteosarcoma, Ewing's sarcoma, unresectable or locally recurrent unresectable chondrosarcoma. Histological diagnosis from initial diagnosis is acceptable for local recurrences, however, biopsy confirmation is strongly recommended. For isolated pulmonary recurrences, biopsy is required. Histological diagnosis will be determined at the treating institution, central review is not required. For patients with chondrosarcoma, determination of unresectable will be made by the treating oncologist and surgeon at the treating institution.

B. Age greater than or equal to 4 years.

C. Measurable Disease-defined as lesions that can be measured in at least one dimension by medical imaging techniques. Ascites, pleural effusions, and bone marrow disease will not be considered measurable disease.

D. Performance Status: Patients greater than or equal to 18 years must have an ECOG performance status of less than or equal to 2. Patients less than 18 years and greater than 10 years must have a Karnofsky Score greater than or equal to 50 percent. Patients less than or equal to 10 years must have Lansky score greater than or equal to 50.

E. Osteosarcoma and Ewing's sarcoma: Patients must have progressed after standard therapy, and may have received no more than 2 additional salvage regimens. Chondrosarcoma: must be unresectable or locally recurrent and unable to be completely resected.

F. Patients must have recovered (defined as toxicity less than grade 2) from toxic effects of all prior therapy before entering onto study.

G. A treatment free interval of at least 2 weeks since the last dose of myelosuppressive therapy is required.

H. At least 6 month interval since last dose of myeloablative therapy or total body irradiation is required.

I. A minimum of 6 weeks since local radiation and 4 months from extensive radiation (greater than 50% of pelvis or cranial spinal radiation) is required.

J. Patients who received filgrastim on a previous cycle of chemotherapy must be off filgrastim for at least 72 hours prior to entry onto study.

K. Adequate bone marrow function with an ANC greater than or equal to 1500/mm3, platelet count greater than or equal to 100,000 mm3 (transfusion independent) and hemoglobin greater than 8.0 g/dl (transfusions permitted).

L. Adequate renal function with serum normal age adjusted serum creatinine (see table below) or creatinine clearance or radioisotope GFR greater than 70 ml/min/1.73 m2. For patients over 18 years of age, creatinine must be less than or equal to upper limit of normal range.

Less than 5 years of age with Maximum Serum Creatinine (mg/dl) of 0.8.

Greater than or equal to 5 and less than or equal to 10 years of age with Maximum Serum Creatinine (mg/dl) of 1.0.

Greater than 10 and less than or equal to 15 years of age with Maximum Serum Creatinine (mg/dl) of 1.2

Greater than 15 and less than or equal to 18 years of age with Maximum Serum Creatinine (mg/dl) of 1.5

M. Patients must have adequate liver function, defined as bilirubin within normal limits, SGPT (ALT) less than or equal to 2.5 x the upper limit of normal. For patients with documented Gilbert Syndrome, total bilirubin greater than ULN may be acceptable if the Principal Investigator in consultation with Medical Affairs, Aventis Oncology approves a special exemption for treatment on this protocol.

N. Neuropathy (Sensory or Motor) due to prior chemotherapy, if present, must be less than or equal to grade 1. Neuropathy (Sensory or Motor) due to prior surgery or tumor involvement must be less than or equal to grade 2 and stable or improving.

O. Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which may include abstinence, while being treated on this study and for 3 months afterwards.

P. Informed consent: All patients or their legal guardians (if the patient is less than 18 years of age) must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study. When appropriate the patient will be included in all discussions in order to obtain assent.

EXCLUSION CRITERIA:

A. Pregnant or breast feeding females

B. Prior treatment with gemcitabine or taxanes

C. Active or uncontrolled infection

D. History of known hypersensitivity reaction to docetaxel or other agents formulated in polysorbate 80.

E. Recipient of prior allogeneic transplants.

Special Instructions:

Currently Not Provided

Keywords:

Antineoplastic Drugs

Refractory Sarcomas

Ewing Sarcoma

Osteosarcoma

Chondrosarcoma

Recruitment Keyword(s):

None

Condition(s):

Osteosarcoma

Sarcoma, Ewing's

Chondrosarcoma

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Gemcitabine

Drug: Docetaxel

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31.

Saylors RL 3rd, Stine KC, Sullivan J, Kepner JL, Wall DA, Bernstein ML, Harris MB, Hayashi R, Vietti TJ; Pediatric Oncology Group. Cyclophosphamide plus topotecan in children with recurrent or refractory solid tumors: a Pediatric Oncology Group phase II study. J Clin Oncol. 2001 Aug 1;19(15):3463-9.

Rischin D, Boyer M, Smith J, Millward M, Michael M, Bishop J, Zalcberg J, Davison J, Emmett E, McClure B. A phase I trial of docetaxel and gemcitabine in patients with advanced cancer. Ann Oncol. 2000 Apr;11(4):421-6.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/13/2009