A multi-arm dose-finding phase Ib multicenter study of imatinib in combination with the oral phosphatidyl-inositol 3-kinase (PI3-K) inhibitor BKM120 in patients with Gastrointestinal Stromal Tumor (GIST) who failed prior therapy with imatinib and sunitinib
- Conditions
- Gastrointestinal Stromal TumorGIST10017990
- Registration Number
- NL-OMON35356
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
1. Male or female patients * 18 years of age
2. WHO performance status of 0-2
3. Histologically confirmed diagnosis of GIST that is unresectable or metastatic
4. Available tissue specimen:
* Dose-escalation part: archival tumor tissue
* Dose-expansion part: plus fresh pre-treatment biopsy.
5. Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or
metastatic GIST:
* Dose-escalation part: treatment failure may be due to disease progression or intolerance.
* Dose-expansion part: documented disease progression on both imatinib and sunitinib, no more than two lines of prior therapy.
6. Radiological (CT/MRI) confirmation of disease progression (RECIST 1.1 criteria) during prior
therapy with imatinib and sunitinib will be required for patients entering the Dose-expansion part
7. At least one measurable lesion, as defined by RECIST version 1.1, will be required for patients
entering the Dose-expansion part.
1. Previous treatment with PI3-K inhibitors
2. A medical history of (as judged by the Investigator or a psychiatrist):
* Active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or thoughts, or homicidal thoughts (immediate risk of doing harm to others)
* * CTCAE grade 3 anxiety
3. Results of questionnaires at screening (see protocol for details, page 32)
4. Poorly controlled diabetes mellitus (HbA1c > 8%)
5. Patient has active cardiac disease or dysfunction, see protocol for details, page 32
6. Known symptomatic brain metastasis
7. History of significant bleeding disorder unrelated to cancer
8. Major surgery within 4 weeks
9. Patients who have received wide field radiotherapy within 4 weeks or limited field radiation for palliation within 2 weeks
10. Patient is currently receiving chronic treatment with steroids or another immunosuppressive agent, strong/moderate CYP3A4 inhibitors/inducers, warfarin, phenytoin, QT prolongators or Torsade de Pointes inducers (see protocol for details and washout)
11. Pregnancy, lactation
12. Females of childbearing potential and males not using safe contraception
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>MTD and/or RP2D</p><br>
- Secondary Outcome Measures
Name Time Method <p>Adverse effects, PK, disease progression</p><br>