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

NCT ID: NCT00089544

Last Updated: 2018-04-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-17
• Study Completion Date: 2013-11-05

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dacarbazine

Intervention Type: DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Filgrastim

Intervention Type: BIOLOGICAL

Given subcutaneously

Ifosfamide

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiotherapy

Thalidomide

Intervention Type: DRUG

Given orally

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgical resection

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiotherapy

Thalidomide

Intervention Type: DRUG

Given orally

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgical resection

Interventions

Dacarbazine

Given IV

Intervention Type: DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Filgrastim

Given subcutaneously

Intervention Type: BIOLOGICAL

Ifosfamide

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Radiation Therapy

Undergo radiotherapy

Intervention Type: RADIATION

Thalidomide

Given orally

Intervention Type: DRUG

Therapeutic Conventional Surgery

Undergo surgical resection

Intervention Type: PROCEDURE

Other Intervention Names

4-(Dimethyltriazeno)imidazole-5-carboxamide; 5-(Dimethyltriazeno)imidazole-4-carboxamide; Asercit; Biocarbazine; Dacarbazina; Dacarbazina Almirall; Dacarbazine - DTIC; Dacatic; Dakarbazin; Deticene; Detimedac; DIC; Dimethyl (triazeno) imidazolecarboxamide; Dimethyl Triazeno Imidazol Carboxamide; Dimethyl Triazeno Imidazole Carboxamide; dimethyl-triazeno-imidazole carboxamide; Dimethyl-triazeno-imidazole-carboximide; DTIC; DTIC-Dome; Fauldetic; Imidazole Carboxamide; Imidazole Carboxamide Dimethyltriazeno; WR-139007; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; FILGRASTIM, LICENSE HOLDER UNSPECIFIED; G-CSF; Neupogen; r-metHuG-CSF; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; Asta Z 4942; Asta Z-4942; Cyfos; Holoxan; Holoxane; Ifex; IFO; IFO-Cell; Ifolem; Ifomida; Ifomide; Ifosfamidum; Ifoxan; IFX; Iphosphamid; Iphosphamide; Iso-Endoxan; Isoendoxan; Isophosphamide; Mitoxana; MJF 9325; MJF-9325; Naxamide; Seromida; Tronoxal; Z 4942; Z-4942; Cancer Radiotherapy; Irradiate; Irradiated; irradiation; RADIATION; Radiotherapeutics; radiotherapy; RT; Therapy, Radiation; (+)-Thalidomide; (-)-Thalidomide; .alpha.-Phthalimidoglutarimide; 2, 6-Dioxo-3-phthalimidopiperidine; Alpha-Phthalimidoglutarimide; Contergan; Distaval; Kevadon; N-(2,6-Dioxo-3-piperidyl)phthalimide; N-Phthaloylglutamimide; N-Phthalylglutamic Acid Imide; Neurosedyn; Pantosediv; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)-; Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)-; Sedalis; Sedoval K-17; Softenon; Synovir; Talimol; Thalomid

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Burton Eisenberg

Role: PRINCIPAL_INVESTIGATOR

Radiation Therapy Oncology Group

Locations

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

NCI-2012-02588

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG-0330

Identifier Type: -

Identifier Source: secondary_id

CDR0000365499

Identifier Type: -

Identifier Source: secondary_id

RTOG-0330

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-0330

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021661

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02588

Identifier Type: -

Identifier Source: org_study_id