Clinical research study to find out if the combination of two study drugs called ribociclib and trametinib is safe and has beneficial effects in people who have solid tumors

Phase 1

Conditions: Solid tumors, Pancreatic Cancer, Colorectal Cancer
MedDRA version: 20.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-005019-34-BE

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 153

Inclusion Criteria

Inclusion Criteria (All):
•Written informed consent must be obtained prior to any study specific
screening procedures
•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
Other protocol-defined inclusion/exclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 91
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 62

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
•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 anticoagulant
•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

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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