- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00089544
Preoperative Thalidomide With Radiation Therapy For Patients With Low-Grade Primary Soft Tissue Sarcoma or Thalidomide With Radiation Therapy and Chemotherapy For Patients With High-Grade or Intermediate-Grade Primary Soft Tissue Sarcoma of the Arm, Leg, or Body Wall
A Pilot Phase II Study of Pre-Operative Radiation Therapy and Thalidomide (IND 48832; NSC 66847) for Low Grade Primary Soft Tissue Sarcoma or Pre-Operative MAID/Thalidomide/Radiation Therapy for High/Intermediate Grade Primary Soft Tissue Sarcoma of the Extremity or Body Wall
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
I. Determine the treatment delivery and toxicity of the combination of thalidomide and radiotherapy in patients with low-grade primary soft tissue sarcoma of the extremity or body wall.
II. Determine the treatment delivery and toxicity of the combination of thalidomide and doxorubicin, ifosfamide, dacarbazine, and radiotherapy in patients with high- or intermediate-grade primary soft tissue sarcoma of the extremity or body wall and compare these results with those of patients treated on RTOG-9514.
III. Determine the feasibility of using specific tissue and circulating biomarkers of antiangiogenic response in patients treated with these regimens, in a multi-institutional setting.
IV. Determine the quantitative changes and patient variabilities of these biomarkers before, during, and after therapy with these regimens.
V. Determine the baseline data sets of biomarkers, particularly circulating endothelial cells, in patients treated with these regimens.
VI. Determine the tolerance to long-term post-operative thalidomide in these patients.
VII. Determine the clinical response to pre-operative therapy in these patients.
VIII. Correlate local control and disease-free survival with surrogate biological endpoints in patients treated with these regimens.
OUTLINE: This is a pilot, cohort study. Patients with high- or intermediate-grade tumors >= 8 cm in diameter are assigned to cohort A and patients with low-grade tumors > 5 cm in diameter are assigned to cohort B.
Cohort A: Patients receive doxorubicin, ifosfamide, and dacarbazine IV continuously on days 1-3, 22-24, and 43-45. Patients receive filgrastim (G-CSF) subcutaneously beginning on days 4, 25, and 46 and continuing until blood counts recover. Patients undergo radiotherapy once daily on days 7-11, 14-18, 21, 28-32, 35-39, and 42. Patients receive oral thalidomide once daily on days 7-21 and 26-42. Patients undergo surgical resection between days 84 and 98. Beginning 2 weeks after surgery, patients receive oral thalidomide once daily for 12 months in the absence of unacceptable toxicity.
Cohort B: Patients receive oral thalidomide once daily beginning on day 1 and continuing until 1 week before surgery. Patients undergo radiotherapy once daily, 5 days a week, on weeks 1-5. Patients undergo surgical resection between days 77 and 91. Beginning 2 weeks after surgery, patients receive oral thalidomide once daily for 6 months in the absence of unacceptable toxicity.
Patients are followed every 3 months for 2 years and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 44 patients (22 per cohort) will be accrued for this study within 17 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19103
- Radiation Therapy Oncology Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Diagnosis of primary soft tissue sarcoma
- T2a or T2b disease
- Superficial or deep tumor
- Grade 1, 2, 3, or 4
- Tumor located on the upper extremity (including shoulder), lower extremity (including hip), or trunk
Meets 1 of the following criteria:
- Tumor ? 8 cm in maximal diameter and grade 3 or 4 (intermediate or high grade) (cohort A)
- Tumor > 5 cm in maximal diameter and grade 1 or 2 (low grade) (cohort B)
- Locally recurrent disease allowed provided there has been no prior radiotherapy to the primary tumor
- No histologically confirmed rhabdomyosarcoma, extraosseous Ewing's primitive neuroectodermal tumors, osteosarcoma or chondrosarcoma, Kaposi's sarcoma, angiosarcoma, desmoid tumors, or dermatofibrosarcoma protuberans
- No overt evidence of lung metastases (CT scan evidence of small incidental lesions without histologic diagnosis allowed)
- No evidence of other metastases
- No sarcoma of the head, neck, intra-abdominal, or retroperitoneal region
- Performance status - Zubrod 0-1
- At least 2 years
- Absolute neutrophil count ? 1,500/mm^3
- Platelet count ? 120,000/mm^3
- Hemoglobin ? 8.0 g/dL (cohort A)
No known hypercoagulable disorders, such as the following:
- APC resistance (factor V Leiden)
- Protein S deficiency
- Protein C deficiency
- Antithrombin III deficiency
- Hyperhomocystinemia
- Dysplasminogenemia
- High plasminogen activator inhibitor
- Dysfibrinogenemia
- Antiphospholipid syndrome
- Thrombocythemia
- Dysproteinemia
- Fibrin split products < 2 times upper limit of normal (ULN)
- Fibrinogen > 200 mg/dL
- Bilirubin ? 1.5 mg/dL (1.0 mg/dL for patients with Gilbert's syndrome)
- AST and ALT ? 2.0 times ULN
- PT and PTT < 1.25 times ULN (except in patients treated with anticoagulants for unrelated medical conditions [e.g., atrial fibrillation])
- No history of hepatic cirrhosis
- Creatinine ? 1.5 mg/dL
- Creatinine clearance > 60 mL/min
- No atherosclerotic coronary artery disease that required bypass surgery within the past year
- No uncompensated coronary artery disease by ECG or physical examination
- No myocardial infarction within the past 6 months
- No severe or unstable angina within the past 6 months
- No uncompensated congestive heart failure
- No New York Heart Association class II-IV heart disease
- No symptomatic peripheral vascular disease
- No history of deep vein thrombosis
Cohort A only:
- EF ? 50% within the past 6 months
- LVEF > 50%
- No pulmonary embolus except if caused directly by foreign body implants (e.g., central venous catheters or portacaths)
- No global neurocognitive symptomatology
- No fatigue ? grade 2
- No history of uncontrolled seizures or uncontrolled seizure disorder
- No sensory neuropathy ? grade 2 except for localized neuropathy due to mechanical cause or trauma
- No other malignancies within the past 3 years except non-invasive malignancies (e.g., carcinoma in situ of the cervix, breast, or oral cavity) or squamous or basal cell skin cancer
- No history of uncontrolled myxedema
- No hypothyroidism ? grade 3
- No active uncontrolled bacterial, viral, or fungal infection
- No other significant illness that would preclude surgery
- No other major illness or psychiatric impairment that would preclude study therapy
- No known AIDS
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use 2 effective barrier methods of contraception for 4 weeks before, during, and for at least 4 weeks after study treatment
- No prior thalidomide
- No prior biologic therapy for this tumor
- No prior chemotherapy for this tumor
- See Disease Characteristics
- No prior radiotherapy for this tumor
- See Cardiovascular
- No other concurrent investigational drugs
- No concurrent sedating drugs
- No concurrent illegal sedating "recreational" drugs
- No concurrent alcohol intake of more than 1 drink per day
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Cohort A (chemotherapy, radiation, thalidomide, surgery)
Patients receive doxorubicin, ifosfamide, and dacarbazine IV continuously on days 1-3, 22-24, and 43-45.
Patients receive G-CSF subcutaneously beginning on days 4, 25, and 46 and continuing until blood counts recover.
Patients undergo radiotherapy once daily on days 7-11, 14-18, 21, 28-32, 35-39, and 42.
Patients receive oral thalidomide once daily on days 7-21 and 26-42.
Patients undergo surgical resection between days 84 and 98. Beginning 2 weeks after surgery, patients receive oral thalidomide once daily for 12 months in the absence of unacceptable toxicity.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given orally
Other Names:
Undergo surgical resection
Undergo radiotherapy
Other Names:
Given subcutaneously
Other Names:
|
EXPERIMENTAL: Cohort B (thalidomide, radiation, surgery)
Patients receive oral thalidomide once daily beginning on day 1 and continuing until 1 week before surgery.
Patients undergo radiotherapy once daily, 5 days a week, on weeks 1-5.
Patients undergo surgical resection between days 77 and 91.
Beginning 2 weeks after surgery, patients receive oral thalidomide once daily for 6 months in the absence of unacceptable toxicity.
|
Correlative studies
Given orally
Other Names:
Undergo surgical resection
Undergo radiotherapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment Delivery With Compliance Defined as Receiving at Least 95% of the Pre-operative Protocol Dose of RT, All 3 Cycles of MAID (if Applicable), and Receive Thalidomide on 75% of the Days During Radiation
Time Frame: Duration of treatment (which can continue up to approximately 15 months).
|
Was to be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.
Due to early study closure, this endpoint could not be fully evaluated per the protocol plan.
|
Duration of treatment (which can continue up to approximately 15 months).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0
Time Frame: From start of treatment to time of surgery
|
Will be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.
|
From start of treatment to time of surgery
|
Response to Pre-operative Therapy Assessed Using RECIST Criteria
Time Frame: From start of treatment to time of surgery.
|
From start of treatment to time of surgery.
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Anti-Bacterial Agents
- Leprostatic Agents
- Adjuvants, Immunologic
- Antibiotics, Antineoplastic
- Thalidomide
- Ifosfamide
- Isophosphamide mustard
- Lenograstim
- Doxorubicin
- Liposomal doxorubicin
- Dacarbazine
- Imidazole
Other Study ID Numbers
- NCI-2012-02588 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- U10CA021661 (U.S. NIH Grant/Contract)
- RTOG-0330 (OTHER: CTEP)
- CDR0000365499
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Adult Soft Tissue Sarcoma
-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI)WithdrawnRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue SarcomaUnited States, Canada
-
National Institutes of Health Clinical Center (CC)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma | Stage IVB Adult Soft Tissue Sarcoma
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
Northwestern UniversityAVEO Pharmaceuticals, Inc.CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)National Comprehensive Cancer NetworkCompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States
-
City of Hope Medical CenterTerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Adult LiposarcomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Recurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue SarcomaUnited States, Canada
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States