http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2004-C-0001.html
NIH Clinical Research Studies
Protocol Number: 04-C-0001
Active Accrual, Protocols Recruiting New Patients
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 Keyword(s):
None
Condition(s):
Osteosarcoma
Sarcoma, Ewing's
Chondrosarcoma
Investigational Drug(s):
None
Investigational Device(s):
None
Intervention(s):
None
Supporting Site:
N/A
Contact(s):
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
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.
Active Accrual, Protocols Recruiting New Patients
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Ann Oncol. 2000 Apr;11(4):421-6. Related Articles, Links
A phase I trial of docetaxel and gemcitabine in patients with
advanced cancer.
Rischin D, Boyer M, Smith J, Millward M, Michael M, Bishop J,
Zalcberg J, Davison J, Emmett E, McClure B.
Division of Haematology and Medical Oncology, Peter MacCallum
Cancer Institute, Melbourne, Australia. drischin@petermac.unimelb.edu.au
BACKGROUND: Docetaxel and gemcitabine are active in a broad range
of malignancies. The objective of this phase I trial was to determine
the maximally tolerated doses of the combination of docetaxel and
gemcitabine. PATIENTS AND METHODS: Patients with advanced cancer, WHO
performance status 0-2, who had received up to one prior chemotherapy
regimen were treated with gemcitabine on days 1 and 8 and docetaxel on
day 8 repeated every 21 days. Prophylactic ciprofloxacin was commenced
on day 11 of each cycle and continued until the neutrophil count
reached 1.0 x 10(9)/l. G-CSF was not administered. Dose levels studied
were docetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200
and 100/1200 mg/m2. RESULTS: Thirty-nine patients were entered and all
were assessable for toxicity. The highest administered dose level was
100 mg/m2 docetaxel and 1200 mg/m2 gemcitabine with dose limiting
toxicities of febrile neutropenia, grade 4 neutropenia > or = 7
days, grade 4 thrombocytopenia, grade 3 stomatitis and/or grade 3
fatigue in three out of six patients. Treatment was well tolerated (40
cycles) in the 10 patients treated at the recommended dose level
(85/1200) with only a single episode of febrile neutropenia and grade 3
or 4 non-hematologic toxicity was infrequent. There was no significant
pulmonary toxicity. Responses were seen in a range of malignancies
including non-small-cell lung cancer. CONCLUSIONS: The recommended dose
level of 85 mg/m2 docetaxel and 1200 mg/m2 gemcitabine has a favourable
toxicity profile and is suitable for further investigation in phase II
trials. This non-platinum containing regimen warrants further
investigation as a potential alternative to platinum containing
regimens in non-small-cell lung cancer and other malignancies.
Publication Types:
* Clinical Trial
* Clinical Trial, Phase I
PMID: 10847460 [PubMed – indexed for MEDLINE]