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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01562899




Registration number
NCT01562899
Ethics application status
Date submitted
22/03/2012
Date registered
26/03/2012
Date last updated
15/02/2017

Titles & IDs
Public title
A Study of MEK162 and AMG 479 in Patients With Selected Solid Tumors
Scientific title
A Phase Ib/II Open-label, Multi-center Study of the Combination of MEK162 Plus AMG 479 (Ganitumab) in Adult Patients With Selected Advanced Solid Tumors
Secondary ID [1] 0 0
2012-000305-76
Secondary ID [2] 0 0
CMEK162X2111
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Pancreatic Adenocarcinoma 0 0
BRAF Mutated Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEK162
Treatment: Drugs - AMG 479

Experimental: Dose escalation - Dose finding group chosen in order to establish a safe and tolerated dose of binimetinib in combination with ganitumab in patients with selected advanced solid tumors.

Experimental: KRAS mutated colorectal adenocarcinoma - Patients with KRAS mutant colorectal cancer.
The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.

Experimental: Metastatic pancreatic adenocarcinoma - Patients with metastatic pancreatic cancer.
The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.

Experimental: BRAF mutated melanoma - Patients with mutant BRAF V600 melanoma.
The starting dose (30 mg bid) of binimetinib chosen for this study was a fraction of the MTD (60 mg bid) and the RP2D (45 mg bid) determined for single agent use. The starting dose for ganitumab was 12 mg/kg q2w which had been shown to be a well-tolerated dose in combination with other anti-cancer agents.


Treatment: Drugs: MEK162
Supplied as tablets of dosage strength 15 mg in high-density polyethylene bottles with child-resistant closure.

Treatment: Drugs: AMG 479
Supplied as sterile liquid for intravenous infusion in vials in boxes. Until April 2013 a frozen formulation with a concentration of 30 mg/ml was used; from May 2013 onwards a refrigerated formulation with a concentration of 70 mg/ml was used.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib: Estimation of Maximum Tolerated Doses (MTDs) and/or recommended Phase II doses (RP2Ds) by measuring incidence of dose limiting toxicities - To estimate the MTDs and/or RP2Ds of MEK162 in combination with AMG479 by measuring incidence of dose limiting toxicities in Cycle 1 (Cycle 1 = 28 days)
Timepoint [1] 0 0
Approximately 6 months
Primary outcome [2] 0 0
Phase II: Antitumor activity of MEK162 in combination with AMG 479 by evaluating Objective Response Rate (ORR) in colorectal carcinoma and melanoma and by evaluating Disease Control Rate (DCR) at week 10 in pancreatic carcinoma - To estimate the antitumor activity of MEK162 in combination with AMG479 by evaluating Objective Response Rate (ORR) according to RECIST 1.1 in colorectal carcinoma and melanoma and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 at week 10 in pancreatic carcinoma
Timepoint [2] 0 0
Approximately 24 months
Secondary outcome [1] 0 0
Both Phases: Safety and tolerability of MEK162 & AMG 479 (ganitumab) in combination by evaluating the adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity - To characterize the safety and tolerability of MEK162 and AMG 479 (ganitumab) in combination by evaluating the incidence and severity of adverse events, serious adverse events (as per CTCAE grading), changes in hematology and chemistry values, vital signs, ECGs; dose interruptions, reductions and dose intensity
Timepoint [1] 0 0
Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Secondary outcome [2] 0 0
Both Phases: Determination of single and multiple dose pharmacokinetics (PK) profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentrations and basic PK parameters of MEK162 - To determine single and multiple dose PK profile of MEK162 in combination with AMG 479 (ganitumab) by measuring time vs. plasma concentration as well as basic PK parameters of MEK162 at different timepoints prior and post study drug combination dosing.
Timepoint [2] 0 0
Phase Ib: Approximately 6 months; Phase II: Approximately 24 months
Secondary outcome [3] 0 0
Phase Ib: Preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Overall Response Rate (ORR), Duration of Response (DOR) and Progression Free Survival (PFS) - To assess preliminary anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating Overall Response Rate (ORR), Duration of Response (DOR), Progression Free Survival (PFS) as assessed by the investigator according to RECIST 1.1
Timepoint [3] 0 0
Approximately 6 months
Secondary outcome [4] 0 0
Phase II: Further anti-tumor activity of MEK162 & AMG 479 (ganitumab) in combination by evaluating the DOR, PFS and OS by evaluating Disease Control Rate for colorectal carcinoma and melanoma; Overall Response Rate for pancreatic carcinoma patients - To further assess the anti-tumor activity of MEK162 and AMG 479 (ganitumab) in combination by evaluating the Duration of Response (DOR) and Progression Free Survival (PFS) per RECIST 1.1 and Overall Survival in all phase II patients and by evaluating the Disease Control Rate (DCR) per RECIST 1.1 for colorectal carcinoma and melanoma and Overall Response Rate (ORR) per RECIST 1.1 for pancreatic carcinoma patients
Timepoint [4] 0 0
Approximately 24 months

Eligibility
Key inclusion criteria
- Patients aged = 18 years

- Patients with advanced solid tumors (CRC, melanoma) with documented somatic KRAS or
BRAFV600 mutations in tumor tissue. Patients with metastatic pancreatic adenocarcinoma
may be enrolled irrespectively of KRAS or BRAFV600 mutational status.

- Patients must have relapsed or progressed following standard therapy or patients for
whom no standard anticancer therapy exists.

- Measurable disease as determined by RECIST v1.1. World Health Organization (WHO)
Performance Status (PS) = 2.

- Adequate organ function

- Negative serum pregnancy test
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy with MEK- or IGF-1R- inhibitor

- History or current evidence of central serous retinopathy (CSR), retinal vein
occlusion (RVO) or retinal degenerative disease

- Patients with known history of severe infusion reactions to monoclonal antibodies

- Patients with primary CNS tumor or CNS tumor involvement

- History of thromboembolic event requiring full-dose anticoagulation therapy

- Clinically significant cardiac disease

- History of another malignancy within 2 years

- Pregnant or nursing (lactating) women

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Utah
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
France
State/province [5] 0 0
Toulouse Cedex 9
Country [6] 0 0
Italy
State/province [6] 0 0
Napoli
Country [7] 0 0
Spain
State/province [7] 0 0
Catalunya
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Array BioPharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, open-label, phase Ib/II study. First, the aim of the phase Ib part is
to estimate the MTD(s) and/or to identify the recommended phase II dose(s) (RP2D) for the
combination of MEK162 and AMG 479 (ganitumab), followed by the phase II part to assess the
clinical efficacy and to further assess the safety of the combination in selected patient
populations. The dose escalation part of the study will be guided by a Bayesian Logistic
Regression Model (BLRM). At least 18 patients are expected to be enrolled in the dose
escalation part.

Following MTD/ RP2D declaration, patients will be enrolled in three phase II arms to assess
efficacy of the combination as well as to better understand the safety, tolerability, PK,
antibody concentrations and PD of the combination at MTD/RP2D. Phase II arm 1 will consist of
approximately 25 patients with KRAS-mutant colorectal adenocarcinoma. Phase II arm 2 will
consist of approximately 20 patients with metastatic pancreatic adenocarcinoma. Phase II arm
3 will consist of approximately 28 patients with mutant BRAFV600 melanoma.

Patients will be treated until progression of disease, unacceptable toxicity develops, or
withdrawal of informed consent, whichever occurs first. All patients will be followed up - at
minimum patients must complete the safety follow-up assessments 30 days after the last dose
of the study treatment.
Trial website
https://clinicaltrials.gov/show/NCT01562899
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Array BioPharma
Address 0 0
303-381-6604
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01562899