A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

NCT01543698

Last updated date
Study Location
H. Lee Moffitt Cancer Center & Research Institute Moffitt SC 2
Tampa, Florida, 33612, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Solid Tumors Harboring a BRAF V600 Mutation
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available

- Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation

- Evidence of measurable disease as determined by RECIST v1.1

- World Health Organization (WHO) Performance Status ≤ 2

- Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


Progressive disease following prior treatment with RAF-inhibitors in combination with
MEK-inhibitors


- Symptomatic or untreated leptomeningeal disease


- Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing
anti-epileptic drugs


- Known acute or chronic pancreatitis


- History or current evidence of retinal disease, retinal vein occlusion or
ophthalmopathy


- Clinically significant cardiac disease


- Patients with abnormal laboratory values at Screening/baseline


- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LGX818/MEK162


- Previous or concurrent malignancy


- Pregnant or nursing (lactating) women


- For addition of LEE011 in the triple combination, congenital long QT syndrome or
family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3,
brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT
>1.5 x ULN.


Other protocol-defined inclusion/exclusion criteria may apply

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Solid Tumors Harboring a BRAF V600 MutationA Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
NCT01543698
  1. Tampa, Florida
  2. Baltimore, Maryland
  3. Boston, Massachusetts
  4. Houston, Texas
  5. Camperdown, New South Wales
  6. North Sydney, New South Wales
  7. Westmead, New South Wales
  8. Leuven,
  9. Montreal, Quebec
  10. Paris, Cedex 10
  11. Milano, MI
  12. Napoli,
  13. Singapore,
  14. Barcelona, Catalunya
  15. Madrid,
  16. St. Gallen,
  17. Zuerich,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
Official Title  ICMJE A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors
Brief Summary This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part to assess the clinical efficacy and to further assess the safety of the combinations in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28 days. The dose escalation parts of the trial will be conducted in adult patients with BRAF V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the dual combination and at least 12 patients for the triple combination. The dose escalation will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D declaration, patients will be enrolled in three Phase II arms for the dual combination and one Phase II arm for the triple combination. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. All patients enrolled in the Phase II part of the study will be followed for survival.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Solid Tumors Harboring a BRAF V600 Mutation
Intervention  ICMJE
  • Drug: LGX818
  • Drug: MEK162
  • Drug: LEE011
Study Arms  ICMJE
  • Experimental: dual combination
    LGX818 QD and MEK162 BID
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
  • Experimental: triple combination
    LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off.
    Interventions:
    • Drug: LGX818
    • Drug: MEK162
    • Drug: LEE011
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 8, 2013)
179
Original Estimated Enrollment  ICMJE
 (submitted: March 2, 2012)
87
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available

  • Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation
  • Evidence of measurable disease as determined by RECIST v1.1
  • World Health Organization (WHO) Performance Status ? 2
  • Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Exclusion Criteria:

Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors

  • Symptomatic or untreated leptomeningeal disease
  • Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs
  • Known acute or chronic pancreatitis
  • History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy
  • Clinically significant cardiac disease
  • Patients with abnormal laboratory values at Screening/baseline
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162
  • Previous or concurrent malignancy
  • Pregnant or nursing (lactating) women
  • For addition of LEE011 in the triple combination, congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ? 3, brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT >1.5 x ULN.

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   France,   Italy,   Singapore,   Spain,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01543698
Other Study ID Numbers  ICMJE CMEK162X2110
2011-005875-17 ( EudraCT Number )
C4221005 ( Other Identifier: Pfizer )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP