Safety, Pharmacokinetics and Pharmacodynamics of BKM120 Plus MEK162 in Selected Advanced Solid Tumor Patients
This study is currently recruiting participants.
Verified May 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01363232
First received: May 24, 2011
Last updated: May 6, 2013
Last verified: May 2013
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Purpose
This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of the orally administered phosphatidylinositol 3'-kinase (PI3K) inhibitor BKM120 in combination with the MEK1/2 inhibitor MEK162. This combination will be explored in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (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 BKM120 and MEK162.
Study drugs will be administered once daily orally on a continuous schedule. A treatment cycle is defined as 28 days.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Solid Tumors, Selected Solid Tumors |
Drug: BKM120 + MEK162 |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: 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 BKM120 Plus MEK162 in Adult Patients With Selected Advanced Solid Tumors |
Resource links provided by NLM:
Genetics Home Reference related topics:
breast cancer
MedlinePlus related topics:
Cancer
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- Incidence of Dose Limiting Toxicities [ Time Frame: during Cycle 1 of treatment with BKM120 and MEK162 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Number of participants with adverse events and serious adverse events. [ Time Frame: from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]
- Overall response rate, duration of response, time to response and progression free survival [ Time Frame: every 8 weeks of treatment ] [ Designated as safety issue: No ]
- Time versus plasma concentration profiles of BKM120 and MEK162 [ Time Frame: during the first cycle of treatment on Cycle 1 Day 1 and Cycle 1 Day 15 ] [ Designated as safety issue: No ]
- Treatment -induced PI3K and MEK/ERK pathway signaling inhibition and evidence of biological activity in tumor. [ Time Frame: during the first cycle of treatment on Cycle 1 Day 15 and at disease progression ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 88 |
| Study Start Date: | August 2011 |
| Estimated Study Completion Date: | February 2014 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: BKM120 + MEK162 | Drug: BKM120 + MEK162 |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- histologically/ cytologically confirmed, advanced non resectable solid tumors
- Measurable or non-measurable, but evaluable disease as determined by RECIST
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01363232
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, Massachusetts | |
| Massachusetts General Hospital Mass General 2 | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Rosemary Boyle 617-724-0865 rboyle1@partners.org | |
| Principal Investigator: Aditya Bardia | |
| United States, Michigan | |
| Wayne State University/Karmanos Cancer Institute Study Coordinator | Recruiting |
| Detroit, Michigan, United States, 48201 | |
| Contact: Angela Powell 313-576-8096 powellan@karmanos.org | |
| Principal Investigator: Patricia M. LoRusso | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center MSKCC (2) | Recruiting |
| New York, New York, United States, 10021 | |
| Contact: Michelle Maziarz 646-227-2125 maziarzm@mskcc.org | |
| Principal Investigator: Mrinal K. Gounder | |
| United States, South Carolina | |
| Cancer Centers of the Carolinas CCC Faris | Recruiting |
| Greenville, South Carolina, United States, 29605 | |
| Contact: Jan Kueber 864-455-3735 jkueber@ghs.org | |
| Principal Investigator: Joe J. Stephenson, Jr. | |
| United States, Texas | |
| MD Anderson Cancer Center/University of Texas MD Anderson PSC | Recruiting |
| Houston, Texas, United States, 77030-4009 | |
| Contact: Rabiul Islam 713-792-7634 rislam@mdanderson.org | |
| Principal Investigator: Filip Janku | |
| Canada, Ontario | |
| Novartis Investigative Site | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Germany | |
| Novartis Investigative Site | Recruiting |
| Essen, Germany, 45147 | |
| Novartis Investigative Site | Recruiting |
| Heidelberg, Germany, 69120 | |
| Netherlands | |
| Novartis Investigative Site | Recruiting |
| Utrecht, Netherlands, 3584CX | |
| Singapore | |
| Novartis Investigative Site | Recruiting |
| Singapore, Singapore, 169610 | |
| Spain | |
| Novartis Investigative Site | Recruiting |
| Sevilla, Andalucía, Spain, 41013 | |
| Novartis Investigative Site | Recruiting |
| Barcelona, Cataluna, Spain, 08035 | |
| Switzerland | |
| Novartis Investigative Site | Recruiting |
| Bellinzona, Switzerland, 6500 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01363232 History of Changes |
| Other Study ID Numbers: | CMEK162X2101, 2011-001083-22 |
| Study First Received: | May 24, 2011 |
| Last Updated: | May 6, 2013 |
| Health Authority: | United States: Food and Drug Administration Germany: Ministry of Health Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) Spain: Ministry of Health |
Keywords provided by Novartis:
|
BKM120, MEK162, RAS RAF mutations, triple negative breast cancer |
pancreatic cancer, ovarian cancer, NSCLC progressed on EGFR TKI PI3K inhibitor, MEK inhibitor |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on June 13, 2013