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

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1.Patient has histologically and/or cytologically confirmed malignancies:
Phase I: advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy 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 and advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies without a standard of care treatment option available.
2. Phase II only: measurable disease.
3. ECOG performance status 0 or 1.
4. Adequate bone marrow and organ function (see protocol 5.2 inclusion criterium 7)
5. 12-lead ECG values (mean of triplicate ECGs): QTcF interval at screening <450 msec (using Fridericia*s correction) and resting heart rate 50-90 bpm
For details see protocol section 4.2 pages 46-47

Exclusion Criteria

1. Phase II only:Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
Phase Ib and Phase II:
2. 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 (with the exception of alopecia).
3. Local therapy to liver * 3 months of C1D1, Local therapy includes surgical resection, radiotherapy, and/or embolization/ablation.
4. History of liver disease as follow: Cirrhosis - Autoimmune hepatitis - Active viral hepatitis - Portal hypertension - Drug induced liver steatosis
5. Prior systemic anti-cancer treatment 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..
6. Warfarin or other Coumadin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
7. History of deep vein thrombosis or pulmonary embolism within 6 months from screening.
8. CNS involvement unless they meet ALL of the criteria specified in protocol bullet 12.
9. Impairment of GI function or GI disease that may significantly alter the absorption of the study drugs
10. A known history of HIV infection
11. History of interstitial lung disease or pneumonitis.
12. Any other concurrent severe or uncontrolled medical condition
13. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality. See details in protocol bullet 17.
14. Currently receiving any of the substances listed in protocol bullet 19 and cannot be discontinued 7 days prior to the start of the study medication.
15. 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.
16. History of retinal vein occlusion.
For detailed description of exclusion criteria see protocol section 4.3 pages 65-68

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Maximum Tolerate Dose (MTD), Recommended Phase 2 Regimen (RP2R), Overall<br /><br>Response Rate</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Safety and tolerability, Pharmacokinetics (PK), Duration of Response (DOR),<br /><br>Disease Control Rate (DCR), Time to overall Response (TTR), Overall Survival<br /><br>(OS), Progression Free Survival (PFS), Clinical Benefit Rate (CBR).</p><br>