ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00089544
Recruitment Status : Terminated
First Posted : August 9, 2004
Results First Posted : July 10, 2013
Last Update Posted : April 13, 2018
Sponsor:
Collaborator:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
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 Drug: Dacarbazine Drug: Doxorubicin Hydrochloride Biological: Filgrastim Drug: Ifosfamide Other: Laboratory Biomarker Analysis Radiation: Radiation Therapy Drug: Thalidomide Procedure: Therapeutic Conventional Surgery Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : June 17, 2004
Actual Primary Completion Date : September 27, 2011
Actual Study Completion Date : November 5, 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Thalidomide

Arm Intervention/treatment
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: Dacarbazine
Given IV
Other 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

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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

Biological: Filgrastim
Given subcutaneously
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Drug: Ifosfamide
Given IV
Other Names:
  • 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

Other: Laboratory Biomarker Analysis
Correlative studies

Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • RADIATION
  • Radiotherapeutics
  • radiotherapy
  • RT
  • Therapy, Radiation

Drug: Thalidomide
Given orally
Other Names:
  • (+)-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

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection

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.
Other: Laboratory Biomarker Analysis
Correlative studies

Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • RADIATION
  • Radiotherapeutics
  • radiotherapy
  • RT
  • Therapy, Radiation

Drug: Thalidomide
Given orally
Other Names:
  • (+)-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

Procedure: Therapeutic Conventional Surgery
Undergo surgical resection




Primary Outcome Measures :
  1. 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). ]
    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 :
  1. Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0 [ Time Frame: From start of treatment to time of surgery ]
    Will be estimated using a binomial distribution and accompanied by the associated 95% confidence interval.

  2. Response to Pre-operative Therapy Assessed Using RECIST Criteria [ Time Frame: From start of treatment to time of surgery. ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00089544


Locations
United States, Pennsylvania
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
National Cancer Institute (NCI)
Radiation Therapy Oncology Group
Investigators
Principal Investigator: Burton Eisenberg Radiation Therapy Oncology Group

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089544     History of Changes
Other Study ID Numbers: NCI-2012-02588
NCI-2012-02588 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG-0330
CDR0000365499
RTOG-0330 ( Other Identifier: Radiation Therapy Oncology Group )
RTOG-0330 ( Other Identifier: CTEP )
U10CA021661 ( U.S. NIH Grant/Contract )
First Posted: August 9, 2004    Key Record Dates
Results First Posted: July 10, 2013
Last Update Posted: April 13, 2018
Last Verified: March 2018

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