Ignite Creation Date:
2024-05-05 @ 4:56 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00359333
Status:
COMPLETED
Last Update Posted:
2013-10-30
First Post:
2006-08-01
Brief Title:
Phase II Trial of Locally AdvancedMetastatic Soft Tissue Sarcoma or AdvancedMetastatic Malignant GIST
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
Multiple Centers Prospective Phase II Trial of Gemcitabine and Docetaxel Combination Chemotherapy in Patients With Locally AdvancedMetastatic Soft Tissue Sarcoma or Imatinib Mesylate Refractory AdvancedMetastatic Malignant Gastrointestinal Stromal Tumor
Status:
COMPLETED
Status Verified Date:
2013-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STS
Brief Summary:
Study Design Type of Study This is an open-label single arm prospective multiple-center phase II study
Duration of the Study Period in One Subject Treatment duration is planned for six cycles unless there is evidence of disease progression or unacceptable toxicity Patients with continued response after six cycles could receive two additional cycles of therapy In case complete response and in the absence of unacceptable toxicity treatment will be continued for at least 2 further cycles to achieve the minimal of 6 total cycles
Study Objectives Primary Objective The primary objective is to determine the response rate of sequential gemcitabine and docetaxel combination in patients with locally advancedmetastatic soft tissue sarcoma or imatinib mesylate refractory GIST
Secondary Objectives The secondary objectives of this study are to determine the time to progression in patients treated with this regimen the toxicity of this regimen in these patients the overall survival and the quality of life
Molecular analysis of genetic aberration in soft tissue sarcoma The genetic aberrations of soft tissue sarcoma as reported in literature will be determined The genetic aberration will be correlated to chemotherapy responses
c-kit and PDGFR gene mutations induced by imatinib mesylate and chemotherapy Those acquired gene mutation of c-kit and PGDFR induced by imatinib mesylate will be first determined We will also examine further gene mutation of c-kit and PGDFR caused by combination chemotherapy
Duration of the Study Period in One Subject Treatment duration is planned for six cycles unless there is evidence of disease progression or unacceptable toxicity Patients with continued response after six cycles could receive two additional cycles of therapy In case complete response and in the absence of unacceptable toxicity treatment will be continued for at least 2 further cycles to achieve the minimal of 6 total cycles
Study Objectives Primary Objective The primary objective is to determine the response rate of sequential gemcitabine and docetaxel combination in patients with locally advancedmetastatic soft tissue sarcoma or imatinib mesylate refractory GIST
Secondary Objectives The secondary objectives of this study are to determine the time to progression in patients treated with this regimen the toxicity of this regimen in these patients the overall survival and the quality of life
Molecular analysis of genetic aberration in soft tissue sarcoma The genetic aberrations of soft tissue sarcoma as reported in literature will be determined The genetic aberration will be correlated to chemotherapy responses
c-kit and PDGFR gene mutations induced by imatinib mesylate and chemotherapy Those acquired gene mutation of c-kit and PGDFR induced by imatinib mesylate will be first determined We will also examine further gene mutation of c-kit and PGDFR caused by combination chemotherapy
Detailed Description:
Eligibility Criteria
Inclusion criteria
Patients must have a histologically confirmed diagnosis of 1 locally advanced unresectable or metastatic soft tissue sarcoma or 2 unresectablemetastatic GIST previously treated with imatinib mesylate and is documented to have drug resistance to imatinib mesylate treatment defined by tumor progression
Age greater than or equal to 18 years and younger than or equal to 70 years old
Measurable disease defined as lesions that can be measured in at least one dimension by physical examination or medical imaging techniques Ascites pleural effusions and bone marrow disease will not considered measurable disease
Patients must have an ECOG performance status of less than or equal to 2 Patients must have recovered defined as toxicity less than grade 2 from toxic effects of all prior therapy before entering onto study
A treatment of drug free interval of at least 4 weeks since the last dose of chemotherapy or imatinib mesylate therapy is required
More than 4 weeks since prior radiotherapy is required Adequate bone marrow function with an ANC greater than or equal to 1500ml platelet count greater than or equal to 100000 ml transfusion independent and hemoglobin greater than or equal to 80 gdl transfusions permitted
Patients must have adequate renal function with serum creatinine less than or equal to 15 mgdl
Patients must have adequate liver function defined as bilirubin within 15 times the upper limit of normal and liver transaminases within 25 times the upper limit of normal
All patients must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study
Exclusion criteria
Patients who have prior treatment with gemcitabine or taxane Pregnant or breast feeding females Active or uncontrolled infection Patients with brain or leptomeningeal metastases
Treatment Plan
For safety and convenience of drug administration a Port-A catheter implantation is required before the start of the first chemotherapy course
Gemcitabine 800 mgm2 will be administered by intravenous infusion over 80 minutes on day 1 and day8 and docetaxel 60 mgm2 over 60 minutes on day 1 of a 21-day cycle After the first cycle of the chemotherapy if the ANC of the patient is always 1500ml before the starting of the next cycle the dosage of docetaxel will be escalated to 75 mgm2 on day 1 of the next and following cycles
All patients received filgrastim 300 mg subcutaneously once per day on day 12 to 15
During treatment complete blood cell counts are performed weekly History and physical examinations and assessment of toxicities are performed before each cycle of treatment
Patients with progressive disease evaluated at the third or sixth course should be suggested salvage treatment and withdrawn from protocol treatment
Patients with SD CR or PR continue on study and undergo repeat CT scan after cycle 6
Patients who have continued response at the sixth course will be given two additional courses of chemotherapy and undergo a CT scan again after cycle 8
Dose Adjustments dose adjustments were required in the following situations
If patients experienced febrile neutropenia or had platelet count of less than 25000ml lasting more than 5 days doses of gemcitabine and docetaxel will be reduced to 75 of the previous dose in all subsequent cycles
If at day 1 of the treatment cycle the ANC is less than 1500ml or if the platelet count is less than 50000ml treatment will be delayed 1 week
Patients in whom the ANC or platelet count has not recovered after a 2-week delay will be removed from the study
If on day 8 the ANC is 500 to 999ul and the platelet is 50000ul gemcitabine are provided at 75 of the day 1 doses
If at day 8 the ANC is less than 500ul or if the platelet count is less than 50000ul gemcitabine at the day 8 dose will not be provided in that cycle
If the patients experience grade 3 or 4 neurotoxicity treatment will be delayed for 1 week If neurotoxicity has resolved to grade 2 treatment resumed with the docetaxel dose decreases to 75 of the previous dose for all subsequent cycles
If the patients bilirubin level is more than 15 mgdL the docetaxel treatment will be hold for that cycle If bilirubin returns to 15 mgdL docetaxel treatment will be resumed in the subsequent cycles
If patients experienced other grade 3 or 4 nonhematologic toxicities except alopecia treatment will be hold for up to 2 weeks treatment will be resumed if nonhematologic toxicity has resolved to grade 2
Criteria for Withdrawal from Study Documented disease progression A new cycle of chemotherapy will be given if ANC 1500ml platelet count 50000 ml transfusion independent and hemoglobin 80 gdl transfusions permitted On the scheduled Day 1 of a new treatment cycle if the hemogram is not yet recovered chemotherapy will be postponed and the patient will be followed weekly until the resolution of toxicity If the interruption is more than 2 weeks from the schedule Day 1 the patient should be taken off protocol treatment
Occurrence of adverse event that the attending physician considers withdrawal from protocol treatment is for the patients optimal benefit
Voluntary withdrawal
Inclusion criteria
Patients must have a histologically confirmed diagnosis of 1 locally advanced unresectable or metastatic soft tissue sarcoma or 2 unresectablemetastatic GIST previously treated with imatinib mesylate and is documented to have drug resistance to imatinib mesylate treatment defined by tumor progression
Age greater than or equal to 18 years and younger than or equal to 70 years old
Measurable disease defined as lesions that can be measured in at least one dimension by physical examination or medical imaging techniques Ascites pleural effusions and bone marrow disease will not considered measurable disease
Patients must have an ECOG performance status of less than or equal to 2 Patients must have recovered defined as toxicity less than grade 2 from toxic effects of all prior therapy before entering onto study
A treatment of drug free interval of at least 4 weeks since the last dose of chemotherapy or imatinib mesylate therapy is required
More than 4 weeks since prior radiotherapy is required Adequate bone marrow function with an ANC greater than or equal to 1500ml platelet count greater than or equal to 100000 ml transfusion independent and hemoglobin greater than or equal to 80 gdl transfusions permitted
Patients must have adequate renal function with serum creatinine less than or equal to 15 mgdl
Patients must have adequate liver function defined as bilirubin within 15 times the upper limit of normal and liver transaminases within 25 times the upper limit of normal
All patients must sign a document of informed consent indicating their awareness of the investigational nature and the risks of the study
Exclusion criteria
Patients who have prior treatment with gemcitabine or taxane Pregnant or breast feeding females Active or uncontrolled infection Patients with brain or leptomeningeal metastases
Treatment Plan
For safety and convenience of drug administration a Port-A catheter implantation is required before the start of the first chemotherapy course
Gemcitabine 800 mgm2 will be administered by intravenous infusion over 80 minutes on day 1 and day8 and docetaxel 60 mgm2 over 60 minutes on day 1 of a 21-day cycle After the first cycle of the chemotherapy if the ANC of the patient is always 1500ml before the starting of the next cycle the dosage of docetaxel will be escalated to 75 mgm2 on day 1 of the next and following cycles
All patients received filgrastim 300 mg subcutaneously once per day on day 12 to 15
During treatment complete blood cell counts are performed weekly History and physical examinations and assessment of toxicities are performed before each cycle of treatment
Patients with progressive disease evaluated at the third or sixth course should be suggested salvage treatment and withdrawn from protocol treatment
Patients with SD CR or PR continue on study and undergo repeat CT scan after cycle 6
Patients who have continued response at the sixth course will be given two additional courses of chemotherapy and undergo a CT scan again after cycle 8
Dose Adjustments dose adjustments were required in the following situations
If patients experienced febrile neutropenia or had platelet count of less than 25000ml lasting more than 5 days doses of gemcitabine and docetaxel will be reduced to 75 of the previous dose in all subsequent cycles
If at day 1 of the treatment cycle the ANC is less than 1500ml or if the platelet count is less than 50000ml treatment will be delayed 1 week
Patients in whom the ANC or platelet count has not recovered after a 2-week delay will be removed from the study
If on day 8 the ANC is 500 to 999ul and the platelet is 50000ul gemcitabine are provided at 75 of the day 1 doses
If at day 8 the ANC is less than 500ul or if the platelet count is less than 50000ul gemcitabine at the day 8 dose will not be provided in that cycle
If the patients experience grade 3 or 4 neurotoxicity treatment will be delayed for 1 week If neurotoxicity has resolved to grade 2 treatment resumed with the docetaxel dose decreases to 75 of the previous dose for all subsequent cycles
If the patients bilirubin level is more than 15 mgdL the docetaxel treatment will be hold for that cycle If bilirubin returns to 15 mgdL docetaxel treatment will be resumed in the subsequent cycles
If patients experienced other grade 3 or 4 nonhematologic toxicities except alopecia treatment will be hold for up to 2 weeks treatment will be resumed if nonhematologic toxicity has resolved to grade 2
Criteria for Withdrawal from Study Documented disease progression A new cycle of chemotherapy will be given if ANC 1500ml platelet count 50000 ml transfusion independent and hemoglobin 80 gdl transfusions permitted On the scheduled Day 1 of a new treatment cycle if the hemogram is not yet recovered chemotherapy will be postponed and the patient will be followed weekly until the resolution of toxicity If the interruption is more than 2 weeks from the schedule Day 1 the patient should be taken off protocol treatment
Occurrence of adverse event that the attending physician considers withdrawal from protocol treatment is for the patients optimal benefit
Voluntary withdrawal
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None