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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02703571




Registration number
NCT02703571
Ethics application status
Date submitted
4/03/2016
Date registered
9/03/2016
Date last updated
10/07/2019

Titles & IDs
Public title
Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
Scientific title
A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors
Secondary ID [1] 0 0
2015-005019-34
Secondary ID [2] 0 0
CTMT212X2106
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Pancreatic Cancer 0 0
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ribociclib
Treatment: Drugs - Trametinib

Experimental: Advanced or metastatic pancreatic cancer - Patients in the Phase II portion of the study who have advanced or metastatic pancreatic cancer

Experimental: KRAS-mutant colorectal cancer - Patients in the Phase II portion of the study who have KRAS-mutant colorectal cancer


Treatment: Drugs: ribociclib


Treatment: Drugs: Trametinib


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

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs) - Phase I part:
The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS.
Timepoint [1] 0 0
21-day cycle one of treatment
Primary outcome [2] 0 0
Objective Response Rate (ORR) - Phase II part:
The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment.
Timepoint [2] 0 0
Until progression of disease up to 1 year
Secondary outcome [1] 0 0
Duration of response (DOR) - Among patients with a confirmed response (PR or CR) per RECIST 1.1, DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause. The distribution function of DOR will be estimated using the Kaplan-Meier method. The median DOR along with 95% CI will be presented by treatment arm.
Timepoint [1] 0 0
Until progression of disease up to 1 year
Secondary outcome [2] 0 0
Time to response - Time to overall response of CR or PR (TTR) is defined as the time from start of study drug to first documented response (CR or PR, which must be confirmed subsequently) for patients with a confirmed CR or PR. TTR will be summarized by treatment arm, using descriptive statistics.
Timepoint [2] 0 0
Until progression of disease up to 1 year
Secondary outcome [3] 0 0
Disease control rate - Disease control rate (DCR) is defined as the proportion of patients with best overall response of CR, PR, or SD per RECIST 1.1. DCR will be estimated and the binomial exact 95% CI will be provided by arm.
Timepoint [3] 0 0
Until progression of disease up to 1 year
Secondary outcome [4] 0 0
Progression disease rate - Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.
Timepoint [4] 0 0
Until progression of disease up to 1 year
Secondary outcome [5] 0 0
Progression free survival - Progression-free survival (PFS) is defined as the time from the date of the first dose of study drug to the date of first documented disease progression per RECIST 1.1 or death due to any cause.
Timepoint [5] 0 0
Until progression of disease up to 1 year
Secondary outcome [6] 0 0
overall survival - Overall survival (OS) is defined as the time from the date of first dose of study drug to the date of death due to any cause.
Timepoint [6] 0 0
Until death up to 1 year

Eligibility
Key inclusion criteria
Inclusion Criteria (All):

- Written informed consent must

- Patient has histologically and/or cytologically confirmed malignancies:

Phase I:

• Patients with advanced or metastatic solid tumors who have failed at least one prior line
of systemic antineoplastic therapy in the advanced setting without a standard of care
treatment option available;

Phase II:

- Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior
systemic antineoplastic therapies in the advanced setting

- Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic
antineoplastic therapies in the advanced setting without a standard of care treatment
option available. Testing for KRAS mutation in patients with CRC using locally
approved diagnostic kit will be used for eligibility.

- Phase II only: patient must have measurable disease

- Patient has an ECOG performance status 0 or 1.

- Patient has adequate bone marrow and organ function

- Patient must have specified laboratory values within normal limits or corrected to
within normal limits with supplements before the first dose of study medication on
Cycle 1 Day 1:

- Standard 12-lead ECG values defined
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Phase II only:

• Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.

Phase I and Phase II:

- Patient with a known hypersensitivity to the study drugs or any of the excipients of
ribociclib or trametinib.

- Patient is concurrently using other anti-cancer therapy.

- Patient has received radiotherapy = 4 weeks or limited field radiation for palliation
= 2 weeks prior to Cycle 1 Day 1

- Patient has received local therapy to liver = 3 months of C1D1

- History of liver disease as follow:

- Cirrhosis

- Autoimmune hepatitis

- Active viral hepatitis

- Portal hypertension

- Drug induced liver steatosis

- Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1

- Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for
doxorubicin or 900 mg/m2 or more for epirubicin.

- Patient is currently receiving warfarin or other coumadin derived anti-coagulant

- Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months
of screening.

- Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day
1, with the exception of adequately treated basal or squamous cell carcinoma or
curatively resected cervical cancer.

- Patients with central nervous system (CNS) involvement

- Patient has impairment of GI function or GI disease that may significantly alter the
absorption of the study drugs

- History of interstitial lung disease or pneumonitis.

- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality

- Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or
Substances that have a narrow therapeutic window and are predominantly metabolized
through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:

- Patient is currently receiving or has received systemic corticosteroids = 2 weeks
prior to starting study drug, or who have not fully recovered from side effects of
such treatment.

- History of retinal vein occlusion (RVO)

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
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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 - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Germany
State/province [10] 0 0
Koeln
Country [11] 0 0
Germany
State/province [11] 0 0
Ulm
Country [12] 0 0
Netherlands
State/province [12] 0 0
Amsterdam
Country [13] 0 0
Netherlands
State/province [13] 0 0
Utrecht
Country [14] 0 0
Spain
State/province [14] 0 0
Catalunya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose
expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer.
Open-label, nonrandomized.
Trial website
https://clinicaltrials.gov/show/NCT02703571
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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
Other publications