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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Radiation Therapy Oncology Group
First posted: 2004-08-09
Enrollment: 23
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Duration of treatment (which can continue up to approximately 15 months).
Secondary outcomes:
measure: Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0
timeFrame: From start of treatment to time of surgery
measure: Response to Pre-operative Therapy Assessed Using RECIST Criteria
timeFrame: From start of treatment to time of surgery.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Radiation Therapy Oncology Group
state: Pennsylvania
Study officials:
affiliation: Radiation Therapy Oncology Group
name: Burton Eisenberg
role: PRINCIPAL_INVESTIGATOR
References: