A Study to Investigate Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BKM120 Plus GSK1120212 in Selected Advanced Solid Tumor Patients
This study is currently recruiting participants.
Verified November 2012 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01155453
First received: June 17, 2010
Last updated: November 26, 2012
Last verified: November 2012
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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 recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
- Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
- Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
- Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced and Selected Solid Tumors |
Drug: BKM120 Drug: GSK1120212 |
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 Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors. |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212 [ Time Frame: in average 1 year ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212 [ Time Frame: in average 1 year ] [ Designated as safety issue: Yes ]
- Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212 [ Time Frame: Assessed during the first Cycle (28 days) of treatment ] [ Designated as safety issue: No ]
- Preliminary anti-tumor activity of the combination [ Time Frame: Assessed every 8 weeks of treatment ] [ Designated as safety issue: No ]
- Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin [ Time Frame: Assessed every 2 weeks during the first cycle, then every 4 weeks ] [ Designated as safety issue: No ]
- Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses [ Time Frame: Assessed at baseline (pre-treatment) ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 105 |
| Study Start Date: | April 2010 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BKM120 + GSK1120212 DE
Dose Escalation
|
Drug: BKM120 Drug: GSK1120212 |
|
Experimental: BKM120 + GSK1120212 NSCLC patients
Advanced RAS or BRAF mutant NSCLC patients
|
Drug: BKM120 Drug: GSK1120212 |
|
Experimental: BKM120 + GSK1120212 ovarian cancer patients
Advanced RAS or BRAF mutant ovarian cancer patients
|
Drug: BKM120 Drug: GSK1120212 |
|
Experimental: BKM120 + GSK1120212 pancreatic cancer patients
Advanced RAS or BRAF mutant pancreatic cancer patients
|
Drug: BKM120 Drug: GSK1120212 |
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 1.0
Exclusion Criteria:
- Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
- Clinically manifested 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: NCT01155453
Contacts
| Contact: Novartis Pharmaceuticals | +1(800)340-6843 |
Locations
| United States, California | |
| UCLA/ University of California Los Angeles Div. of Hematology/Oncology | Recruiting |
| Los Angeles, California, United States, 90095 | |
| Contact: Maggie Lindenbaum 310-825-4493 mlindenbaum@mednet.ucla.edu | |
| Principal Investigator: Zev A. Wainberg | |
| United States, Texas | |
| MD Anderson Cancer Center/University of Texas Dept of MD Anderson (8) | Recruiting |
| Houston, Texas, United States, 77030-4009 | |
| Contact: Lacey McQuinn 713-792-9869 lmcquinn@mdanderson.org | |
| Principal Investigator: Filip Janku | |
| Belgium | |
| Novartis Investigative Site | Recruiting |
| Leuven, Belgium, 3000 | |
| Canada, Ontario | |
| Novartis Investigative Site | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Spain | |
| Novartis Investigative Site | Recruiting |
| Sevilla, Andalucía, Spain, 41013 | |
| Novartis Investigative Site | Recruiting |
| Barcelona, Cataluña, 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: | NCT01155453 History of Changes |
| Other Study ID Numbers: | CBKM120B2101, 2009-017157-35 |
| Study First Received: | June 17, 2010 |
| Last Updated: | November 26, 2012 |
| Health Authority: | United States: Food and Drug Administration Canada: Health Canada Spain: Ministry of Health Switzerland: Swissmedic |
Keywords provided by Novartis:
|
BKM120 RAS RAF mutations, triple negative breast cancer, |
pancreatic cancer, PI3K inhibitor, MEK inhibitor |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on May 21, 2013