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

NCT00089544 | Terminated Phase 2 Results

• 4 other identifiers: NCI-2012-02588RTOG-0330CDR0000365499U10CA021661
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (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

  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.

  Duration of treatment (which can continue up to approximately 15 months).

Secondary Outcomes (2)

• Wound Complication (Grades 2, 3, 4, and 5) as Measured by CTCAE v3.0

  From start of treatment to time of surgery

• Response to Pre-operative Therapy Assessed Using RECIST Criteria

  From start of treatment to time of surgery.

Study Arms (2)

Cohort A (chemotherapy, radiation, thalidomide, surgery)

EXPERIMENTAL

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; Drug: Doxorubicin Hydrochloride; Biological: Filgrastim; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Radiation: Radiation Therapy; Drug: Thalidomide; Procedure: Therapeutic Conventional Surgery

Cohort B (thalidomide, radiation, surgery)

EXPERIMENTAL

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; Radiation: Radiation Therapy; Drug: Thalidomide; Procedure: Therapeutic Conventional Surgery

Interventions

Dacarbazine DRUG

Given IV

Also known as: 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

Cohort A (chemotherapy, radiation, thalidomide, surgery)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Cohort A (chemotherapy, radiation, thalidomide, surgery)

Filgrastim BIOLOGICAL

Given subcutaneously

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Cohort A (chemotherapy, radiation, thalidomide, surgery)

Ifosfamide DRUG

Given IV

Also known as: 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

Cohort A (chemotherapy, radiation, thalidomide, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Cohort A (chemotherapy, radiation, thalidomide, surgery); Cohort B (thalidomide, radiation, surgery)

Radiation Therapy RADIATION

Undergo radiotherapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, RADIATION, Radiotherapeutics, radiotherapy, RT, Therapy, Radiation

Cohort A (chemotherapy, radiation, thalidomide, surgery); Cohort B (thalidomide, radiation, surgery)

Thalidomide DRUG

Given orally

Also known as: (+)-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

Cohort A (chemotherapy, radiation, thalidomide, surgery); Cohort B (thalidomide, radiation, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Cohort A (chemotherapy, radiation, thalidomide, surgery); Cohort B (thalidomide, radiation, surgery)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Radiation Therapy Oncology Group: collaborator

Study Sites (1)

Radiation Therapy Oncology Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Dacarbazine; Doxorubicin; Filgrastim; Granulocyte Colony-Stimulating Factor; Ifosfamide; Radiotherapy; Radiation; Thalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Therapeutics; Physical Phenomena; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

This study closed early due to unacceptably high rate of thromboembolic events in Cohort A and due to low accrual in Cohort B. For this reason efficacy endpoints other than response to pre-operative therapy were not reported.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: Radiation Therapy Oncology Group (RTOG)

wseiferheld@acr.org

Study Officials

• Burton Eisenberg

  Radiation Therapy Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2004
• First Posted: August 9, 2004
• Study Start: June 17, 2004
• Primary Completion: September 27, 2011
• Study Completion: November 5, 2013
• Last Updated: April 13, 2018
• Results First Posted: July 10, 2013

Record last verified: 2018-03

Locations

US (1)