Protocol Number: 04-C-0001

Title:

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

Number:

04-C-0001

Summary:

This study will examine the side effects and possible benefits of the anti-cancer drugs gemcitabine (Gemzar ) and docetaxel (Taxere ) in patients with bone or soft tissue cancer (sarcoma); determine how the body absorbs and eliminates the drugs; and perform genetic studies on the tumor and try to grow the tumor in the laboratory or in animals.

Patients 10 years of age and older with recurrent osteosarcoma, Ewing's sarcoma, and inoperable or recurrent inoperable chondrosarcoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, and CT or MRI scans, or both.

Participants receive gemcitabine and docetaxel in 21-day cycles as follows:

- Gemcitabine is given as a 90-minute infusion on days 1 and 8 of each cycle through a catheter (thin plastic tube) placed in an arm vein.

- Docetaxel is given as a 60-minute infusion following the gemcitabine infusion on day 8 of each cycle.

- Filgrastim is given as an injection under the skin either: 1) daily, beginning the day after each docetaxel infusion and continuing until the bone marrow is recovered from chemotherapy (usually 7 to 10 days); or 2) in a long-acting form on the day after the docetaxel infusion. Filgrastim boosts production of blood cells that have been depleted as a result of chemotherapy. Patients are taught to self-administer the injections.

Treatment will continue for a total of 14 cycles or until the patient's tumor gets larger, side effects are unacceptable, the patient decides to stop treatment, or further treatment would not be in the patient's best interest.

In addition to taking the study drugs, patients undergo the following tests and procedures:

- Placement of temporary (IV line) or semi-permanent (Hickman, Broviac, or Port-a-Cath) catheters for giving chemotherapy and other drugs and for drawing blood samples.

- History and physical examination before each dose of chemotherapy to assess health status and drug side effects.

- Blood tests to measure blood counts, liver and kidney function, and electrolyte levels.

- Blood sampling for pharmacology studies on days 1 and 8 of treatment cycle 1 (6 samples on day 1; 11 samples on day 8) to study how the body handles gemcitabine and docetaxel.

- Imaging studies that may include x-rays, CT scans, MRI scans, nuclear medicine scans, and bone scans

- Tumor genetic studies. Tumor samples from patients who require surgery to remove a tumor will be grown in a test tube or in animals to define what genes are expressed (turned on) in the tumor.

At the end of chemotherapy, patients will be monitored for treatment side effects and disease progress, initially every 3 months and then every 6 months until 2 years from finishing treatment

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

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 or equal to 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 Keywords:

None

Conditions:

Osteosarcoma

Sarcoma, Ewing's

Chondrosarcoma

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

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.

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