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MEK162 for Patients With RAS/RAF/MEK Activated Tumors (SIGNATURE)

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ClinicalTrials.gov Identifier: NCT01885195
Recruitment Status : Completed
First Posted : June 24, 2013
Last Update Posted : June 6, 2017
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Brief Summary:
The purpose of this signal seeking study is to determine whether treatment with MEK162 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study

Condition or disease Intervention/treatment Phase
Solid Tumor and Hematologic Malignancies Drug: MEK162 Phase 2

Detailed Description:

This is a phase II, open label study to determine the efficacy and safety of treatment with MEK162 in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have activations of the RAS/RAF/MEK pathway and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. This is a signal-seeking study to match patients with mutations in RAF, RAS, NF1 or MEK to the ATP-noncompetitive MEK 1/2 inhibitor, MEK162. Pre-identification of these mutations or activations in the pathway will be performed locally at a CLIA certified laboratory prior to screening for participation on the trial.

Once the patient has been identified, treating physicians who are qualified investigators may contact Novartis to consider enrollment in this study. For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with single agent MEK162. The patient may not receive any additional anti-cancer therapy during treatment with MEK162.

Patients will continue to receive study treatment until disease progression (assessed by RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (per RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML and MM patients). Scans will be assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up.)


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 3 - MEK162 for Patients With RAS/RAF/MEK Activated Tumors
Study Start Date : October 2013
Actual Primary Completion Date : October 2015
Actual Study Completion Date : April 11, 2017


Arm Intervention/treatment
Experimental: MEK162
MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.
Drug: MEK162
MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.




Primary Outcome Measures :
  1. Clinical benefit rate associated with MEK162 treatment [ Time Frame: 16 weeks ]
    Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria will apply


Secondary Outcome Measures :
  1. Overall Response (OR) or Partial Response (PR) or greater [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply.

  2. Progression-Free Survival (PFS) [ Time Frame: every 8 weeks until death, assessed up to 24 months ]
    Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause

  3. Overall survival (OS) [ Time Frame: every 8 weeks until death, assessed up to 36 months ]
    Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause

  4. Duration of Response (DOR) [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    The duration of response (PR or greater) applies only to patients whose best response was PR or greater. It is defined as the Ttime from the first documented response to the date first documented disease progression or relapse or death due to any cause

  5. Number of participants with adverse events as a measure of Safety and Tolerability [ Time Frame: baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months ]
    Safety and tolerability will be will be based on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges. Other safety data (e.g., electrocardiogram, vital signs) will be considered as appropriate.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has a confirmed diagnosis of a select solid tumor (except for primary diagnosis of pancreatic cancer, biliary cancer, colorectal cancer, low grade serous ovarian cancer, melanoma) or hematologic malignancy (except for primary diagnosis of chronic myelomonocytic leukemia).
  • Patients must be pre-identified as having a tumor with a mutation in RAF, RAS, NF1 or MEK at a CLIA certified laboratory
  • Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
  • Patient must have progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

  • Patient has received prior treatment with MEK162.
  • Patients with primary CNS tumor or CNS tumor involvement
  • History of retinal degenerative disease
  • History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
  • Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist
  • Patients who have neuromuscular disorders that are associated with elevated CK

Information from the National Library of Medicine

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): NCT01885195


  Show 68 Study Locations
Sponsors and Collaborators
Array BioPharma
Investigators
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Study Director: Array BioPharma 303-381-6604

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Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01885195     History of Changes
Other Study ID Numbers: CMEK162AUS11
First Posted: June 24, 2013    Key Record Dates
Last Update Posted: June 6, 2017
Last Verified: May 2017
Keywords provided by Array BioPharma:
RAS, RAF, MEK, NF1, MEK162, signature, papillary thyroid, small intestine, bladder, esophagus, lung cancer, NSCLC, acute myelogenous leukemia, AML
Additional relevant MeSH terms:
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Neoplasms