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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089544
First received: August 6, 2004
Last updated: May 15, 2013
Last verified: May 2013

August 6, 2004
May 15, 2013
June 2004
September 2011   (final data collection date for primary outcome 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 [ Time Frame: Duration of treatment (which can continue up to approximately 15 months). ] [ Designated as safety issue: No ]
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.
Not Provided
Complete list of historical versions of study NCT00089544 on ClinicalTrials.gov Archive Site
  • Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0 [ Time Frame: From start of treatment to time of surgery ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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

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

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 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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Adult Soft Tissue Sarcoma
  • Stage I Adult Soft Tissue Sarcoma
  • Stage II Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • Drug: dacarbazine
    Given IV
    Other Names:
    • DIC
    • DTIC
    • DTIC-Dome
  • Biological: filgrastim
    Given subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
  • Radiation: radiation therapy
    Undergo radiotherapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Drug: thalidomide
    Given orally
    Other Names:
    • Kevadon
    • Synovir
    • THAL
    • Thalomid
  • Procedure: therapeutic conventional surgery
    Undergo surgical resection
  • Other: laboratory biomarker analysis
    Correlative studies
  • 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 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.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: ifosfamide
    • Drug: dacarbazine
    • Biological: filgrastim
    • Radiation: radiation therapy
    • Drug: thalidomide
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Radiation: radiation therapy
    • Drug: thalidomide
    • Procedure: therapeutic conventional surgery
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
23
Not Provided
September 2011   (final data collection date for primary outcome measure)

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
  • 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 ≤ 1.5 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 or 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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00089544
NCI-2012-02588, RTOG-0330, U10CA021661, CDR0000365499
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Burton Eisenberg Radiation Therapy Oncology Group
National Cancer Institute (NCI)
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP