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 10033604 Term: Pancreatic cancer System Organ Class: 100000016908
MedDRA version: 20.0 Level: LLT Classification code 10049280 Term: Solid tumour System Organ Class: 100000020962
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)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-005019-34-ES

Lead Sponsor: ovartis Farmacéutica, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 69

Inclusion Criteria

? Written informed consent must be obtained prior to any study specific screening procedures.
? Patient is an adult male/female = 18 years of age at the time of informed consent.
? Patient has histologically and/or cytologically confirmed malignancies:
Phase Ib:
? 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 therapy 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, i.e., at least one measurable lesion as per response evaluation criteria in solid tumors (RECIST) 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy will only be considered measurable if disease progression at the treated site after completion of prior therapy is clearly documented).
? Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
? Patient has adequate bone marrow and organ function as defined by the following laboratory values within 2 weeks prior to Cycle 1 Day 1 as assessed by local laboratory for eligibility
? Absolute neutrophil count = 1.5 × 109/L (without administration of white blood cell growth factor for at least 2 weeks prior to Cycle 1 Day 1)
? Platelets = 100 × 109/L (without platelet infusion / transfusion for at least 2 weeks prior to Cycle 1 Day 1)
? Hemoglobin = 9.0 g/dL
? INR = 1.5
? Serum creatinine <1.5 mg/dL
? Total bilirubin ? Aspartate aminotransferase (AST) must be within normal range, except for patients with liver metastasis, who are only included if the AST is <2.5 × ULN
? Alanine aminotransaminase (ALT) must be within normal range, except for patients with liver metastasis, who are only included if the ALT is <2.5 × ULN
? Albumin = 3.0 g/dL
? Patient must have the following 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:
? Sodium
? Potassium
? Magnesium
? Phosphorus
? Total Calcium (corrected for serum albumin)
? Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central ECG reading
? QTcF interval at screening <450 msec (using Fridericia’s correction)
? Resting heart rate 50-90 bpm

Further inclusion criteria and details are described in the protocol.
Are the trial

Exclusion Criteria

Phase II only:
? Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
Phase Ib 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, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia) and/or from whom = 25% (Ellis 1961) of the bone marrow was irradiated.
? Limitation of local therapy in liver lesions (localized liver therapy)
? Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, or vaccine therapy) within 28 days prior to Cycle 1 Day 1, or chemotherapy without delayed toxicity within the last 2 weeks preceding the first dose of study treatment with no more than grade 1 treatment related AEs.
? 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 coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
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 unless they meet ALL of the following criteria:
? At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment.
? Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases.
? Patient has impairment of GI function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome, or small bowel resection).
? History of interstitial lung disease or pneumonitis.
? History of liver disease as follow :
? Cirrhosis
? Autoimmune hepatitis
? Portal Hypertension
? Drug-induced liver steatosis
? Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
? History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
? Documented cardiomyopathy
? Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
? Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
? Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically signif

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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