INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme

Completed · Phase 1

Conditions studied: Glioblastoma Multiforme, Gliosarcoma, Colorectal Cancer, Renal Cell Carcinoma

In brief

The purpose of this study is to determine whether the combination of two agents, INC280 and bevacizumab, is safe and effective when administered to patients with Glioblastoma Multiforme (GBM) who have progressed after receiving prior therapy or who have unresectable GBM.

Key facts

Study ID

NCT02386826

Run by

SCRI Development Innovations, LLC

People needed

65

Starts

2015-09-22

Expected to finish

2023-08-23

Last updated by the study team

2023-09-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• KEY POINTS:
• Dose Escalation Phase: Histologic diagnosis of GBM or gliosarcoma. Progressed during or after standard 1st-line therapy for GBM. Patients scheduled to undergo a repeat primary surgical resection are also eligible. Measurable disease as measured by RANO (Response Assessment in Neuro-Oncology) criteria.
• Dose Expansion Phase:
• Cohort A: Histologic diagnosis of GBM. Patients should have progressed during or after standard 1st-line therapy. Patients scheduled to undergo a repeat primary surgical resection are also eligible. Measurable disease as measured by RANO criteria.
• At least 5 patients must have an alteration of MET [as assessed by fluorescence in situ hybridization (FISH) (c-MET/centromere ratio ≥2, or c-MET gene copy number ≥ 5) or RT-PCR or Met immunohistochemistry (IHC) score of 2-3+ or a mutation].
• Cohort B: Histologic diagnosis of GBM patients who have progressed during or after 2nd-line therapy with bevacizumab or a bevacizumab-based regimen. Measurable disease according to RANO criteria.
• Cohort C: Histologic diagnosis of GBM by stereotactic biopsy in patients with unresectable brain tumors.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 or Karnofsky Performance Scale (KPS) of at least 70%.
• Adequate hematologic, renal and liver function
• Life expectancy ≥ 3 months
• Availability of archived tumor samples and/or willingness to provide tissue samples if resection is done. (Fresh tissue biopsy is not required if archival tissue is not available.)

You may not qualify if…

• Prior treatment with bevacizumab for GBM patients eligible for Cohorts A and C. (Prior treatment with bevacizumab is permitted for GBM patients eligible for Cohort B only.)
• Most recent chemotherapy ≤ 21 days to the start of treatment and ≥ Grade 2 chemotherapy-related side effects with the exception of alopecia.
• Use of any investigational drug ≤ 21 days to the start of treatment or 5 half-lives (whichever is shorter) prior to the first dose of INC280 with bevacizumab. For study drugs for which 5 half-lives is ≤ 21 days, a minimum of 10 days between termination of the study drug and the start of treatment is required.
• Uncontrolled seizures (Patients with a history of seizures are eligible if they are currently without seizures on a stable dose of anti-epileptic drugs for 14 days prior to enrollment.)
• History of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
• Major surgery ≤ 28 days to the start of treatment, or subcutaneous venous access device placement ≤ 7 days to the start of treatment
• A serious non healing wound, ulcer, or bone fracture ≤ 28 days to the start of treatment
• Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤ 28 days or limited field radiation for palliation ≤ 7 days prior to starting study drug or has not recovered from side effects of such therapy.
• Leptomeningeal metastases or spinal cord compression due to disease.
• Women of child-bearing potential.
• Receiving drugs known to be strong inhibitors or inducers of CYP3A4 and cannot be discontinued 7 days prior to the start of INC280 treatment and during the course of the study, or medications that are known CYP3A4, CYP1A2, CYP2C8, CYP2C9 or CYP2C19 substrates with narrow therapeutic index, and cannot be discontinued during the course of the study.
• Treatment with proton pump inhibitors within three days prior to study entry.
• Cardiac disease currently or less than 6 months from baseline screening
• Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels must have their blood pressure (BP) controlled with medication prior to starting treatment).
• Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin is allowed.

Where it is running

• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States
• Yale School of Medicine — New Haven, Connecticut, United States
• HCA Midwest - Kansas City — Kansas City, Missouri, United States
• Oklahoma University Health Science Center — Oklahoma City, Oklahoma, United States
• Tennessee Oncology PLLC — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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