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
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| ClinicalTrials.gov Identifier: NCT00089544 |
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Recruitment Status :
Terminated
First Posted : August 9, 2004
Results First Posted : July 10, 2013
Last Update Posted : April 13, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Adult Soft Tissue Sarcoma Stage I Adult Soft Tissue Sarcoma AJCC v7 Stage II Adult Soft Tissue Sarcoma AJCC v7 Stage III Adult Soft Tissue Sarcoma AJCC v7 | Drug: Dacarbazine Drug: Doxorubicin Hydrochloride Biological: Filgrastim Drug: Ifosfamide Other: Laboratory Biomarker Analysis Radiation: Radiation Therapy Drug: Thalidomide Procedure: Therapeutic Conventional Surgery | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 23 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | June 17, 2004 |
| Actual Primary Completion Date : | September 27, 2011 |
| Actual Study Completion Date : | November 5, 2013 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Dacarbazine
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Biological: Filgrastim Given subcutaneously
Other Names:
Drug: Ifosfamide Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Radiation: Radiation Therapy Undergo radiotherapy
Other Names:
Drug: Thalidomide Given orally
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgical resection |
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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.
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Other: Laboratory Biomarker Analysis
Correlative studies Radiation: Radiation Therapy Undergo radiotherapy
Other Names:
Drug: Thalidomide Given orally
Other Names:
Procedure: Therapeutic Conventional Surgery Undergo surgical resection |
- 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.
- 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.
- Response to Pre-operative Therapy Assessed Using RECIST Criteria [ Time Frame: From start of treatment to time of surgery. ]
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| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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
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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)
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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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00089544
| United States, Pennsylvania | |
| Radiation Therapy Oncology Group | |
| Philadelphia, Pennsylvania, United States, 19103 | |
| Principal Investigator: | Burton Eisenberg | Radiation Therapy Oncology Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00089544 |
| Other Study ID Numbers: |
NCI-2012-02588 NCI-2012-02588 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) RTOG-0330 CDR0000365499 RTOG-0330 ( Other Identifier: Radiation Therapy Oncology Group ) RTOG-0330 ( Other Identifier: CTEP ) U10CA021661 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 9, 2004 Key Record Dates |
| Results First Posted: | July 10, 2013 |
| Last Update Posted: | April 13, 2018 |
| Last Verified: | March 2018 |
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Sarcoma Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Thalidomide Doxorubicin Liposomal doxorubicin Ifosfamide Isophosphamide mustard Dacarbazine Imidazole Lenograstim Sargramostim Antibiotics, Antineoplastic Antineoplastic Agents |
Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Alkylating Alkylating Agents Immunosuppressive Agents Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents |