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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02703571
Ethics application status
Date submitted
4/03/2016
Date registered
9/03/2016

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 for Phase Ib 0 0
Pancreatic Cancer for Phase II 0 0
Colorectal Cancer for Phase II 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 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose limiting toxicities (DLTs)
Timepoint [1] 0 0
21-day cycle one of treatment
Primary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
Until progression of disease up to 1 year
Secondary outcome [1] 0 0
Duration of response (DOR)
Timepoint [1] 0 0
Until progression of disease up to 1 year
Secondary outcome [2] 0 0
Time to response
Timepoint [2] 0 0
Until progression of disease up to 1 year
Secondary outcome [3] 0 0
Disease control rate
Timepoint [3] 0 0
Until progression of disease up to 1 year
Secondary outcome [4] 0 0
Progression disease rate
Timepoint [4] 0 0
Until progression of disease up to 1 year
Secondary outcome [5] 0 0
Progression free survival
Timepoint [5] 0 0
Until progression of disease up to 1 year
Secondary outcome [6] 0 0
overall survival
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
Sex
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
NA
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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/09/2019
Sample size
Target
Accrual to date
Final
95
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02703571