NCT02065063

A Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Anti-Cancer Activity of Trametinib in Combination With Palbociclib in Subjects With Solid Tumors

Completed Phase 1 Last updated 1 June 2018

What this trial tests

Phase 1 trial testing Trametinib in Cancer in 28 participants. Completed in 23 June 2016.

Timeline

22 April 2014

Primary endpoint
23 June 2016

23 June 2016

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	28
Start date	22 April 2014
Primary completion	23 June 2016
Estimated completion	23 June 2016
Sites	3 locations across United States

Drugs / interventions tested

• Trametinib (trametinib) — full drug profile →
• Palbociclib (Palbociclib) — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This is a dose-escalation, Phase I/II, open-label, three-part study. Part 1 is designed to determine the recommended dose and schedule for the orally administered MEK inhibitor trametinib, given together with the CDK4/6 inhibitor palbociclib in subjects with solid tumors. Multiple dose levels of each inhibitor will be tested to determine the recommended dose and schedule. Part 2 will evaluate the effect of the combination on tumor biomarkers safety, and anti-cancer activity in subjects with cutaneous melanoma that do not have a change at BRAFV600. Approximately 100-200 subjects will be enrolled. All subjects will receive trametinib and/or palbociclib until disease progression, death, consent withdrawal or unacceptable adverse event (AE).

Data was only collected and analyzed for the Phase I component of the study, the Phase II component of the study was terminated without data collection

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting CDK4 and CDK6: From Discovery to Therapy.
   Sherr CJ, Beach D, Shapiro GI. · · 2016 · cited 729× · PMID 26658964 · DOI 10.1158/2159-8290.cd-15-0894
2. Senescence as a therapeutically relevant response to CDK4/6 inhibitors.
   Wagner V, Gil J. · · 2020 · cited 117× · PMID 32541838 · DOI 10.1038/s41388-020-1354-9
3. Combined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms.
   Olmez I, Brenneman B, Xiao A, Serbulea V, et al · · 2017 · cited 94× · PMID 28814434 · DOI 10.1158/1078-0432.ccr-17-0803
4. Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine.
   Knudsen ES, O'Reilly EM, Brody JR, Witkiewicz AK. · · 2016 · cited 91× · PMID 26385075 · DOI 10.1053/j.gastro.2015.08.056
5. Strategies to tackle RAS-mutated metastatic colorectal cancer.
   Patelli G, Tosi F, Amatu A, Mauri G, et al · · 2021 · cited 65× · PMID 34044286 · DOI 10.1016/j.esmoop.2021.100156
6. Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma.
   Olmez I, Zhang Y, Manigat L, Benamar M, et al · · 2018 · cited 57× · PMID 29844123 · DOI 10.1158/0008-5472.can-17-3124
7. Molecular pathways: targeting NRAS in melanoma and acute myelogenous leukemia.
   Johnson DB, Smalley KS, Sosman JA. · · 2014 · cited 51× · PMID 24895460 · DOI 10.1158/1078-0432.ccr-13-3270
8. Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant Melanoma.
   Cohen JV, Sullivan RJ. · · 2019 · cited 42× · PMID 30992297 · DOI 10.1158/1078-0432.ccr-18-0836