A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors
This study is currently recruiting participants.
Verified February 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01449058
First received: October 6, 2011
Last updated: February 25, 2013
Last verified: February 2013
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Purpose
This is a multi-center, open-label, dose-finding, phase Ib study to estimate the maximum tolerated dose(s) (MTD(s)) and/or recommended dose(s) for expansion (RDE(s)) for the orally administered combination of BYL719 and MEK162. This combination will be explored in adult patients with advanced CRC, esophageal cancer, pancreatic cancer, NSCLC or other advanced solid tumors with documented RAS or BRAF mutations. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. At MTD or RDE, three expansion arms will be opened in order to further assess the safety and preliminary activity of the combination of BYL719 and MEK162 in specific patient populations.
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced and Selected Solid Tumors |
Drug: BYL719 plus MEK162 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study 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 Orally Administered MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Incidence of Dose Limiting Toxicities (DLT) [ Time Frame: during the first cycle (28 days) of treatment with BYL719 and MEK162 ] [ Designated as safety issue: Yes ]Toxicity will be assessed using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 unless otherwise specified. A DLT is defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days following the first dose of BYL719 and MEK162 (Cycle 1), and meets any of the protocol-specified DLT criteria.
Secondary Outcome Measures:
- Number of participants with adverse events and serious adverse events [ Time Frame: Assessed from Cycle 1 Day 1 until treatment discontinuation ] [ Designated as safety issue: Yes ]All AEs and SAEs will be collected in accordance with the protocol and assessed for relatedness to study drug combination.
- Overall response rate [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR).
- Time to progression [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient has not had an event, time to progression is censored at the date of last adequate tumor assessment.
- Progression free survival [ Time Frame: Assessed every 8 weeks until disease progression ] [ Designated as safety issue: No ]Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
- Time versus plasma concentration profiles of BYL719 and MEK162 [ Time Frame: Assessed during the first cycle of treatment ] [ Designated as safety issue: No ]Blood concentrations of MEK162 and its metabolite (AR00426032) and BYL719 will be assessed during the first cycle of treatment.
- Correlation of baseline mutation or amplification status (PIK3CA, KRAS, NRAS and BRAF) and clinical anti-tumor activity outcome [ Time Frame: Assessed at Baseline (pre-treatment) ] [ Designated as safety issue: No ]Collect baseline genetic mutation/alteration status to investigate the potential relationship to anti-tumor activity.
| Estimated Enrollment: | 63 |
| Study Start Date: | April 2011 |
| Estimated Study Completion Date: | March 2014 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BYL719 + MEK162
BYL719 plus MEK162. Dose escalation with a starting dose for the first cohort of 200mg QD BYL719 and 30mg BID MEK162
|
Drug: BYL719 plus MEK162
BYL719 plus MEK162 administered in this dose escalation study until MTD/RDE is achieved, followed by a dose expansion phase.
|
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 solid tumors
- Measurable disease as determined by RECIST 1.1
Exclusion Criteria:
- Primary CNS tumor or CNS tumor involvement
- Diabetes mellitus
- Unacceptable ocular/retinal conditions
- Clinically significant cardiac disease or impaired cardiac function
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01449058
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, Massachusetts | |
| Massachusetts General Hospital CCPO | Recruiting |
| Boston, Massachusetts, United States, 02114 | |
| Contact: Dejan Juric, M.D. 617-724-4000 | |
| Principal Investigator: Dejan Juric | |
| United States, Utah | |
| University of Utah / Huntsman Cancer Institute Huntsman (3) | Recruiting |
| Salt Lake City, Utah, United States, 84103 | |
| Contact: Marlene Mitchell marlene.mitchell@hci.utah.edu | |
| Principal Investigator: Sunil Sharma | |
| Australia, Victoria | |
| Novartis Investigative Site | Recruiting |
| Parkville, Victoria, Australia, 3050 | |
| France | |
| Novartis Investigative Site | Recruiting |
| Villejuif Cedex, France, 94805 | |
| Spain | |
| Novartis Investigative Site | Recruiting |
| Barcelona, Cataluna, Spain, 08035 | |
| United Kingdom | |
| Novartis Investigative Site | Recruiting |
| Sutton, United Kingdom, SM2 5PT | |
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: | NCT01449058 History of Changes |
| Other Study ID Numbers: | CMEK162X2109, 2011-002578-21 |
| Study First Received: | October 6, 2011 |
| Last Updated: | February 25, 2013 |
| Health Authority: | United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration (TGA) France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Spain: Spanish Agency of Medicines United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Novartis:
|
Advanced solid tumor, dose escalation, RAS/BRAF mutation, PI3K inhibitor, |
MEK inhibitor, BYL719, MEK162 |
Additional relevant MeSH terms:
|
Neoplasms |
ClinicalTrials.gov processed this record on May 16, 2013