Clinical trial NCT02164240 (phase 1, status: active, not recruiting)
Conditions: gastrointestinal stromal tumor
ICD codes: C49.A0, C49.A1, C49.A2, C49.A5, C49.A3, C49.A4, C49.A9
Drugs: sunitinib, regorafenib
SMILES: CNC(=O)C1=C(SC2=CC=C3C(NN=C3\C=C\C3=CC=CC=N3)=C2)C=CC=C1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age at the time of study entry.

          -  Histologically confirmed metastatic and/or unresectable GIST. Patients must
             demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line
             and beyond). Any number of previous therapies for GIST is allowed.

          -  Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area
             is ineligible to be considered as measurable disease unless there is objective
             evidence of progression of the lesion prior to study enrollment.

          -  ECOG performance status 0 or 1 (see Appendix A).

          -  Participants must have adequate organ and marrow function as outlined in the protocol.

          -  Patients must be able to swallow oral medication.

          -  Willingness to use effective means of birth control throughout the duration of
             clinical study and for at least 3 months after completion of study drug.

          -  Women of childbearing potential must have a negative pregnancy test performed within 7
             days of the start of study drug administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Use of any approved tyrosine kinase inhibitors or investigational agents within 2
             weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study
             drugs.

          -  Patients with intolerance to sunitinib and/or regorafenib.

          -  Participants who have had radiotherapy within 4 weeks prior to study entry.

          -  Major surgery, or significant traumatic injury within 4 weeks prior to study entry.

          -  Presence of symptomatic or uncontrolled brain or central nervous system metastases.

          -  Known or suspected allergy to the investigational agent or any agent given in
             association with this trial.

          -  Individuals with a history of a different malignancy, other than cervical cancer in
             situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if
             they have been disease-free for at least 5 years, and are deemed by the investigator
             to be at low risk for recurrence of that malignancy OR other primary malignancy is
             neither currently clinically significant nor requiring active intervention.

          -  Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic
             therapy (excluding beta blockers or digoxin). Patients with controlled atrial
             fibrillation are not excluded.

          -  History of clinically significant cardiac disease or congestive heart failure > NYHA
             class 2 (See Appendix C). Patients must not have unstable angina (anginal symptoms at
             rest) or new-onset angina within the last 3 months or myocardial infarction within the
             past 6 months.

          -  Hypertension as defined by systolic blood pressure >140 mmHg or diastolic blood
             pressure > 90 mmH despite optimal medical management.

          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within the 6 months before start of study medication (except for adequately treated
             catheter-related venous thrombosis occurring more than 1 month before the start of
             study medication).

          -  Patients with evidence or history of any bleeding diathesis, irrespective of severity.

          -  Ongoing infection ≥ Grade 2.

          -  Patients with any seizure disorder requiring medication.

          -  Non-healing wound, ulcer, or bone fracture.

          -  Persistent proteinuria Grade 2 or higher measured by urine protein:creatinine ratio on
             a urine sample or during 24-hour assessment.

          -  HIV-positive individuals on combination antiretroviral therapy.

          -  Patients with active hepatitis B or C, or chronic hepatitis B or C requiring treatment
             with antiviral therapy.

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent.

          -  Uncontrolled intercurrent illness.

          -  Pregnant or lactating females.

          -  Presence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol.

          -  Strong CYP3A4 inhibitors within 28 days or 5 drug half-lives, whichever is longer,
             before start of study drug.