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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

Status
Terminated
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00089544
Enrollment
23
Registered
2004-08-09
Start date
2004-06-17
Completion date
2013-11-05
Last updated
2018-04-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Brief summary

Thalidomide may stop the growth of soft tissue sarcoma by stopping blood flow to the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and dacarbazine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving thalidomide together with radiation therapy and/or chemotherapy before surgery may shrink the tumor so that it can be removed. This phase II trial is studying how well giving preoperative (before surgery) thalidomide together with radiation therapy works in treating patients with low-grade primary soft tissue sarcoma, and how well giving thalidomide together with radiation therapy, doxorubicin, ifosfamide, and dacarbazine works in treating patients with high-grade or intermediate-grade primary soft tissue sarcoma of the arm, leg, chest wall, or abdominal wall.

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.

Interventions

DRUGDacarbazine

Given IV

DRUGDoxorubicin Hydrochloride

Given IV

BIOLOGICALFilgrastim

Given subcutaneously

DRUGIfosfamide

Given IV

OTHERLaboratory Biomarker Analysis

Correlative studies

RADIATIONRadiation Therapy

Undergo radiotherapy

DRUGThalidomide

Given orally

PROCEDURETherapeutic Conventional Surgery

Undergo surgical resection

Sponsors

Radiation Therapy Oncology Group
CollaboratorNETWORK
National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
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 RadiationDuration 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.

Secondary

MeasureTime frameDescription
Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0From start of treatment to time of surgeryWill be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.
Response to Pre-operative Therapy Assessed Using RECIST CriteriaFrom start of treatment to time of surgery.

Countries

United States

Participant flow

Participants by arm

ArmCount
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 28-42. 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.
15
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.
7
Total22

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyIneligible10

Baseline characteristics

CharacteristicCohort A (Chemotherapy, Radiation, Thalidomide, Surgery)Cohort B (Thalidomide, Radiation, Surgery)Total
Age, Continuous49.0 years47.0 years48 years
Sex: Female, Male
Female
7 Participants2 Participants9 Participants
Sex: Female, Male
Male
8 Participants5 Participants13 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
15 / 157 / 7
serious
Total, serious adverse events
9 / 153 / 7

Outcome results

Primary

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

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.

Time frame: Duration of treatment (which can continue up to approximately 15 months).

Population: Eligible patients who started study treatment.

ArmMeasureGroupValue (NUMBER)
Cohort A (Chemotherapy, Radiation, Thalidomide, Surgery)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 RadiationNot Compliant5 participants
Cohort A (Chemotherapy, Radiation, Thalidomide, Surgery)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 RadiationCompliant10 participants
Cohort B (Thalidomide, Radiation, Surgery)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 RadiationNot Compliant2 participants
Cohort B (Thalidomide, Radiation, Surgery)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 RadiationCompliant5 participants
Secondary

Response to Pre-operative Therapy Assessed Using RECIST Criteria

Time frame: From start of treatment to time of surgery.

Population: This analysis was not carried out due to the small number of patients accrued to the study. See section Limitations and Caveats.

Secondary

Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0

Will be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.

Time frame: From start of treatment to time of surgery

Population: This analysis was not carried out due to the small number of patients accrued to the study. See section Limitations and Caveats.

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026