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 29, 2014
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: ifosfamide
Drug: dacarbazine
Biological: filgrastim
Radiation: radiation therapy
Drug: thalidomide
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 23
Study Start Date: June 2004
Study Completion Date: December 2012
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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.
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

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

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089544

Locations
United States, Pennsylvania
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Burton Eisenberg Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089544     History of Changes
Other Study ID Numbers: NCI-2012-02588, NCI-2012-02588, CDR0000365499, RTOG-0330, RTOG-0330, U10CA021661
Study First Received: August 6, 2004
Results First Received: March 13, 2013
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Doxorubicin
Ifosfamide
Liposomal doxorubicin
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014