Safety, Pharmacokinetics and Pharmacodynamics of BEZ235 Plus MEK162 in Selected Advanced Solid Tumor Patients
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| ClinicalTrials.gov Identifier: NCT01337765 |
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Recruitment Status
:
Completed
First Posted
: April 19, 2011
Last Update Posted
: February 12, 2016
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This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or RP2D of the orally administered PI3K/mTOR inhibitor BEZ235 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with EGFR mutant NSCLC which has progressed on EGFR inhibitors and triple negative breast cancer, as well as pancreatic cancer, colorectal cancer, malignant melanoma, NSCLC, and other advanced solid tumors with KRAS, NRAS, and/or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RP2D, two expansion arms will be opened in order to further assess safety and preliminary anti-tumor activity of the combination of BEZ235 and MEK162.
Study drugs will be administered orally on a continuous schedule, MEK162 bid and BEZ235 qd, a treatment cycle is defined as 28 days.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Unspecified Adult Solid Tumor, Protocol Specific Solid Tumor | Drug: BEZ235 + MEK162 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 29 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase Ib, Open-label, Multi-center, Dose-escalation and Expansion Study of an Orally Administered Combination of BEZ235 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors |
| Study Start Date : | July 2011 |
| Actual Primary Completion Date : | March 2013 |
| Actual Study Completion Date : | March 2013 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: BEZ235 + MEK162 | Drug: BEZ235 + MEK162 |
- Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BEZ235 and MEK162 ]A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination
- Number of participants with adverse events and serious adverse events [ Time Frame: from Cycle 1 Day 1 until treatment discontinuation ]A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination
- Overall response rate, duration of response, time to response and progression free survival [ Time Frame: every 8 weeks of treatment ]
- Time versus plasma concentration profiles of BEZ235 and MEK162 [ Time Frame: during the first cycle of treatment ]A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination
- Treatment-induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor [ Time Frame: during the first cycle of treatment and at disease progression ]A complete treatment cycle is defined as 28 days of daily continuois treatment with study drug combination
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- histologically/cytologically confirmed, advanced non resectable solid tumors
- Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
Exclusion Criteria:
- Patients with primary CNS tumor or CNS tumor involvement
- Diabetes mellitus - Unacceptable ocular/retinal conditions
Other protocol-defined inclusion/exclusion criteria may apply
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): NCT01337765
| United States, Massachusetts | |
| Massachusetts General Hospital Mass General 2 | |
| Boston, Massachusetts, United States, 02114 | |
| United States, Texas | |
| University of Texas/MD Anderson Cancer Center MD Anderson PSC | |
| Houston, Texas, United States, 77030-4009 | |
| Australia, Victoria | |
| Novartis Investigative Site | |
| Parkville, Victoria, Australia, 3050 | |
| Canada, Ontario | |
| Novartis Investigative Site | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| France | |
| Novartis Investigative Site | |
| Villejuif Cedex, France, 94805 | |
| Spain | |
| Novartis Investigative Site | |
| Barcelona, Cataluña, Spain, 08035 | |
| Study Director: | Array BioPharma | 303-381-6604 |
| Responsible Party: | Array BioPharma |
| ClinicalTrials.gov Identifier: | NCT01337765 History of Changes |
| Other Study ID Numbers: |
CMEK162X2103 2011-000421-74 ( EudraCT Number ) |
| First Posted: | April 19, 2011 Key Record Dates |
| Last Update Posted: | February 12, 2016 |
| Last Verified: | February 2016 |
Keywords provided by Array BioPharma:
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BEZ235, MEK162 RAS RAF mutations, triple negative breast cancer pancreatic cancer, |
NSCLC progressed on EGFR TKI PI3K/mTOR inhibitor, MEK inhibitor Advanced and selected solid tumors |
Additional relevant MeSH terms:
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Neoplasms Dactolisib Antineoplastic Agents |