Proton Chemoradiotherapy for High-Risk Soft Tissue Sarcomas

Phase 2

Withdrawn

• Conditions: Soft Tissue Sarcomas
• Interventions: Procedure: Proton Chemoradiotherapy followed by surgery; Drug: Chemoradiotherapy Temozolomide; Radiation: Proton therapy

• Registration Number: NCT00881595
• Lead Sponsor: University of Florida

Brief Summary

The goal of this study is to evaluate the effects of temozolomide and radiation combination in the treatment intended of soft tissue sarcomas.

This study will also look at the tumor tissue that was removed during your initial biopsy and your final surgery for information that may help to treat soft tissue sarcoma in the future. In addition the investigators will examine a sample of your normal tissue (optional) from the inside of your mouth/cheek (to compare it to your tumor tissue) before starting treatment.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-04-13
• Study First Submitted QC: 2009-04-14
• Study First Posted: 2009-04-15
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-09
• Last Update Posted: 2017-02-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Patients must have histologic and radiographic proof of localized high-risk soft tissue sarcoma (STS) required prior to registration.

• For the purpose of this study, high risk STS is defined by at least two of the following risk factors:

  • Tumor ≥ 5 cm in maximal diameter on MRI or CT
  • Histology grade 3 or 4 (AJCC, 7th edition)
  • Tumor deep to the investing fascia
  • Locally recurrent sarcoma with no prior radiation therapy to the primary site
  • Age >55 years old

• Tumor must be considered potentially resectable as defined by cross sectional imaging.

• At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have ≤ grade 1 acute toxicities of any prior treatment with anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.

• Age ≥18 years at time of consent.

• Physician documented life expectancy of greater than 3 months.

• Patients must have normal organ and marrow function within 4 weeks prior to study treatment as defined below:

  • hemoglobin ≥ 9 g/dL
  • leukocytes ≥3,000/microliter (mcL)
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • total bilirubin ≤ institutional upper limit of normal
  • aspartate aminotransferase (AST/SGOT) and alanine aminotransferase(ALT/SGPT) < 2.5 x institutional upper limit of normal
  • creatinine within 1.5 x upper limit of normal(ULN)

• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 12 months after treatment. Patients must have a negative serum pregnancy test within 14 days prior to beginning treatment on this trial. Sexually active men must also use appropriate contraception method and should not father a child while receiving therapy during this study.

• Ability to understand and the willingness to sign a written Institutional Review Board(IRB) stamped, study specific informed consent document prior to any research related procedures or study treatment.

Exclusion Criteria

• Receiving any investigational agents.
• Treatment with cytotoxic agents and/or treatment with biologic agents within the 4 weeks prior to beginning treatment on this study.
• Evidence of metastatic disease.
• Previous radiotherapy to the affected site.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, and/or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because the investigational agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated.
• HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents.
• All herbal and/or alternative medications should be discontinued while on study, these include but are not limited to: Hydrastis canadensis (goldenseal), Uncaria tomentosa (cat's claw) or Echinacea angustifolia.
• Requirement for treatment with immunosuppressive agents or chronic steroids.
• A history of a hypersensitivity reaction to any of temozolomide's components or to Dacarbazine(DTIC).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Proton Chemoradiotherapy followed by surgery	Proton Chemoradiotherapy followed by surgery	Proton Chemoradiotherapy followed by surgery. Temozolomide five days per week during radiotherapy for 5 weeks. Proton radiation five days per week for 5 weeks Standard surgery will take place 4-6 weeks after completion of chemoradiation.
Chemoradiotherapy Temozolomide	Chemoradiotherapy Temozolomide	Chemoradiotherapy Temozolomide: 75 mg/m2 five days per week during radiotherapy for 5 weeks. Temozolomide should be taken orally 1 hour before each session of radiotherapy during weekdays (Monday through Friday). The dose will be determined using the body surface area (BSA) calculated at the beginning of the concurrent treatment. The BSA will be calculated from the height obtained at the pretreatment visit and the weight obtained before the first day of treatment. The concurrent treatment will last until the end of radiotherapy.
Proton Therapy	Proton therapy	50 cobalt gray equivalent(CGE), 25 daily fractions, 5 weeks (2 CGE/fx)

Primary Outcome Measures

Name	Time	Method
Assess treatment feasibility of neoadjuvant temozolomide-based proton chemoradiotherapy for high-risk soft tissue sarcoma	6 months after surgery then every 6 months for 3 years

Secondary Outcome Measures

Name	Time	Method
Evaluate acute and late toxicities	Weekly during treatment, 6 months after surgery, then every 6 months for 3 years