Clinical Trials /

Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)

NCT03556384

Description:

Funding Source - FDA OOPD FDA-approved products for patients with unresectable or metastatic GIST include therapies such as imatinib and sunitinib. Although there are FDA-approved products for the treatment of advanced/metastatic GIST, these therapies are known to be ineffective in the SDH-mutant/deficient subtype and no known effective therapies exist. The purpose of this study is to investigate SDH-Mutant/Deficient Gastrointestinal Stromal cancer's response to the drug Temozolomide (TMZ) and aim to improve patient outcomes. Temozolomide is approved by the FDA for the treatment of newly diagnosed glioblastoma multiforme (GBM) and refractory anaplastic astrocytoma cancers. Temozolomide is considered experimental because it is not approved by the FDA for the treatment of SDH-Mutant/Deficient Gastrointestinal Stromal Tumor.

Related Conditions:
  • Gastrointestinal Stromal Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
  • Official Title: An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)

Clinical Trial IDs

  • ORG STUDY ID: 180114
  • SECONDARY ID: FD-R-6334
  • NCT ID: NCT03556384

Conditions

  • Gastrointestinal Stromal Tumors
  • Sdh
  • GIST
  • Cancer

Interventions

DrugSynonymsArms
TemozolomideTEMODAR®TMZ 85 mg/m2 mg orally

Purpose

Funding Source - FDA OOPD FDA-approved products for patients with unresectable or metastatic GIST include therapies such as imatinib and sunitinib. Although there are FDA-approved products for the treatment of advanced/metastatic GIST, these therapies are known to be ineffective in the SDH-mutant/deficient subtype and no known effective therapies exist. The purpose of this study is to investigate SDH-Mutant/Deficient Gastrointestinal Stromal cancer's response to the drug Temozolomide (TMZ) and aim to improve patient outcomes. Temozolomide is approved by the FDA for the treatment of newly diagnosed glioblastoma multiforme (GBM) and refractory anaplastic astrocytoma cancers. Temozolomide is considered experimental because it is not approved by the FDA for the treatment of SDH-Mutant/Deficient Gastrointestinal Stromal Tumor.

Detailed Description

      This oncology study will be a phase 2 study for patients with advanced or metastatic GIST.
      This study will determine overall response rate at 6 months for TMZ therapy in patients with
      SDH-mutant/deficient GIST.

      Treatment will continue for 6 months (with option to continue if benefiting treatment) or
      until disease progression or unacceptable toxicity (whichever occurs first). All patients
      will have regular evaluations for assessment of safety parameters. Temozolomide dose may be
      held and/or modified for the management of adverse treatment effects according to
      pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to
      assess tumor resection.

      An end of treatment visit for clinical evaluations and safety assessments will be performed
      approximately 28 days (7 days) after the last dose of study drug. Patients discontinuing
      study treatment will be followed every 3-6 months for disease recurrence and survival.
    

Trial Arms

NameTypeDescriptionInterventions
TMZ 85 mg/m2 mg orallyExperimentalTMZ 85 mg/m2 mg orally once for 21 days followed by 7 days without treatment in 28 day cycles. Treatment will continue for 6 months (with option to continue if benefiting treatment) or until disease progression or unacceptable toxicity (whichever occurs first). All patients will have regular evaluations for assessment of safety parameters. Temozolomide dose may be held and/or modified for the management of adverse treatment effects according to pre-specified criteria. Patients will have radiographic imaging (CT or MRI) every 8 weeks to assess tumor resection. An end of treatment visit for clinical evaluations and safety assessments will be performed approximately 28 days after the last dose of study drug. Patients discontinuing study treatment will be followed every 3-6 months for disease recurrence and survival.
  • Temozolomide

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has pathologically confirmed SDH-mutant/deficient GIST.

          2. Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
             or radiotherapy.

          3. Patient has an ECOG Performance Status of 0-2.

          4. Patient has adequate hematologic, hepatic and renal function.

          5. Female patient of childbearing potential has a negative serum or urine pregnancy
             within 72 hours prior to receiving the first dose of study medication.

          6. Female patient of childbearing potential agrees to use 2 methods of birth control or
             be surgically sterile, or abstain from heterosexual activity for the course of the
             study through 120 days after the last dose of study medication.

          7. Male patient with a partner of childbearing potential agrees to use an adequate method
             of contraception starting with the first dose of study therapy through 120 days after
             the last dose of study therapy.

          8. Has measurable or evaluable disease as per RECIST v1.1 (Appendix B).

          9. Life expectancy of >12 weeks.

        Exclusion Criteria:

          1. Patients who have had major surgery within 4 weeks of initiation of study medication.

          2. Patients who are receiving other concurrent anti-neoplastic therapy (e.g.,
             chemotherapy, targeted therapy, immunotherapy, or radiotherapy) at the start of study
             treatment.

          3. Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          4. Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated
             respiratory, cardiac (including life threatening arrhythmias)].

          5. Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia
             (if applicable) unless agreed that the patient can be entered after discussion with
             the Medical Monitor.

          6. Presence of cardiac impairment class III and IV definitions; OR history of myocardial
             infarction/active ischemic heart disease within one year of study entry; OR
             uncontrolled dysrhythmias; OR poorly controlled angina.

          7. Pregnant or breast-feeding females.

          8. Medical condition such as uncontrolled infection (including HIV), uncontrolled
             diabetes mellitus or cardiac disease which, in the opinion of the treating physician,
             would make this protocol unreasonably hazardous for the patient.

          9. Any concurrent condition which in the investigator's opinion makes it undesirable for
             the subject to participate in this trial or which would jeopardize compliance with the
             protocol.

         10. Patients who cannot swallow oral formulations of the agent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:6 months
Safety Issue:
Description:To determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:4 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:4 years
Safety Issue:
Description:
Measure:Adverse events related to TMZ
Time Frame:6 months
Safety Issue:
Description:Description, grade [CTCAE v4.03], and seriousness

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Adam Burgoyne, MD, PhD

Trial Keywords

  • cancer
  • Temozolomide
  • GIST
  • SDH-Mutant/Deficient
  • SDH
  • Succinate Dehydrogenase

Last Updated

June 24, 2020