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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02703571
Registration number
NCT02703571
Ethics application status
Date submitted
4/03/2016
Date registered
9/03/2016
Date last updated
21/12/2020
Titles & IDs
Public title
Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
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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
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Secondary ID [1]
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2015-005019-34
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Secondary ID [2]
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CTMT212X2106
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Solid Tumors for Phase Ib
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Pancreatic Cancer for Phase II
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Colorectal Cancer for Phase II
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Condition category
Condition code
Cancer
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Bowel - Back passage (rectum) or large bowel (colon)
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Cancer
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Pancreatic
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - ribociclib
Treatment: Drugs - Trametinib
Experimental: Advanced or metastatic solid tumors - Patients in the Phase I portion of the study who have advanced or metastatic solid tumors
Treatment: Drugs: ribociclib
Combination treatment with LEE and TMT
Treatment: Drugs: Trametinib
Combination treatment with LEE and TMT
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence of dose limiting toxicities (DLTs)
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Assessment method [1]
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Phase Ib 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.
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Timepoint [1]
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21-day cycle one of treatment
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Primary outcome [2]
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Objective Response Rate (ORR)
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Assessment method [2]
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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.
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Timepoint [2]
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Until progression of disease up to 1 year
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Secondary outcome [1]
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Duration of response (DOR)
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Assessment method [1]
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Phase II part:
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.
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Timepoint [1]
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Until progression of disease up to 1 year
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Secondary outcome [2]
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Time to response
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Assessment method [2]
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Phase II part:
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.
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Timepoint [2]
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Until progression of disease up to 1 year
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Secondary outcome [3]
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Disease control rate
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Assessment method [3]
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Phase II part:
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.
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Timepoint [3]
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Until progression of disease up to 1 year
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Secondary outcome [4]
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Progression disease rate
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Assessment method [4]
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Phase Ib part:
Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.
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Timepoint [4]
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Until progression of disease up to 1 year
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Secondary outcome [5]
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Progression free survival
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Assessment method [5]
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Phase Ib and phase II parts:
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.
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Timepoint [5]
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Until progression of disease up to 1 year
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Secondary outcome [6]
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overall survival
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Assessment method [6]
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Phase Ib and phase II parts:
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.
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Timepoint [6]
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Until death up to 1 year
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
29/06/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
24/09/2019
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Sample size
Target
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Accrual to date
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Final
95
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Novartis Investigative Site - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Arkansas
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Country [2]
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United States of America
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State/province [2]
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California
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Country [3]
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United States of America
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State/province [3]
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Connecticut
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Country [4]
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United States of America
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State/province [4]
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Florida
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Country [5]
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United States of America
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State/province [5]
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Massachusetts
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Country [6]
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United States of America
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State/province [6]
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Texas
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Country [7]
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Belgium
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State/province [7]
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Leuven
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Country [8]
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Canada
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State/province [8]
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Alberta
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Country [9]
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Canada
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State/province [9]
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British Columbia
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Country [10]
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Germany
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State/province [10]
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Koeln
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Country [11]
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Germany
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State/province [11]
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Ulm
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Country [12]
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Netherlands
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State/province [12]
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Amsterdam
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Country [13]
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Netherlands
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State/province [13]
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Utrecht
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Country [14]
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Spain
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State/province [14]
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Catalunya
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02703571
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02703571
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