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

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ClinicalTrials.gov Identifier: NCT03556384
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : November 12, 2018
Sponsor:
Information provided by (Responsible Party):
Adam Burgoyne, MD, PhD, University of California, San Diego

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Sdh GIST Cancer Drug: Temozolomide Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST)
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2024


Arm Intervention/treatment
Experimental: TMZ 85 mg/m2 mg orally

TMZ 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.

Drug: Temozolomide

Temozolomide 85 mg/m2 will be administered orally 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

Other Name: TEMODAR®




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: 6 months ]
    To determine overall response rate at 6 months for TMZ therapy in patients with SDH-mutant/deficient GIST


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 4 years ]
  2. Overall survival [ Time Frame: 4 years ]
  3. Adverse events related to TMZ [ Time Frame: 6 months ]
    Description, grade [CTCAE v4.03], and seriousness



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03556384


Contacts
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Contact: Adam M Burgoyne, MD, PhD (858) 822-3092 aburgoyne@ucsd.edu
Contact: Jason Sicklick, MD 858-822-6173 jsicklick@ucsd.edu

Locations
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United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Elaine Eng       e1eng@ucsd.edu   
Principal Investigator: Adam M Burgoyne, MD, PhD         
Sub-Investigator: Jason K Sicklick, MD         
Sponsors and Collaborators
Adam Burgoyne, MD, PhD
Investigators
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Principal Investigator: Adam Burgoyne, MD, PhD University of California, San Diego
Principal Investigator: Jason Sicklick, MD University of California, San Diego

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Responsible Party: Adam Burgoyne, MD, PhD, Assistant Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03556384     History of Changes
Other Study ID Numbers: 180114
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Adam Burgoyne, MD, PhD, University of California, San Diego:
cancer
Temozolomide
GIST
SDH-Mutant/Deficient
SDH
Succinate Dehydrogenase
Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents