Safety and Tolerability Study of GSK1120212, a MEK Inhibitor, in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel

Study Overview
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Brief Summary
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The purpose of this study is to determine what dose of GSK1120212 can be given safely in combination with at least one other drug that is already approved to treat cancer. This study will test the safety of up to 6 different GSK1120212 study treatment combinations (GSK1120212 plus either docetaxel, erlotinib, pemetrexed, pemetrexed + carboplatin, pemetrexed + cisplatin, or nab-paclitaxel). The doses identified in this study may be used in future trials to test whether the combination treatment is a safe and effective therapy for subjects with metastatic lung and/or pancreatic cancers.

Official Title
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An Open-Label, Phase I/Ib Dose Escalation Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel in Subjects With Advanced Solid Tumors

Conditions
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Cancer

Intervention / Treatment
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* Drug: Trametinib (GSK1120212)
* Drug: Docetaxel
* Drug: Erlotinib
* Drug: Pemetrexed
* Drug: Carboplatin
* Drug: nab-Paclitaxel
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has a solid tumor. Expansion cohorts are limited to non-small cell lung cancer and/or pancreatic cancer with or without a KRAS mutation. Tumor progression following at least one prior standard therapy, the subject refuses standard therapy, or no standard therapy exists. The subject has a radiographically measurable tumor. The subject is able to carry out daily life activities without difficulty. The subject is able to swallow and retain oral medication. The subject does not have significant side effects from previous anti-cancer treatment. The subject has adequate organ and blood cell counts. Sexually active subjects must use medically acceptable methods of contraception during the course of the study. Exclusion Criteria: The subject has had major surgery or received certain types of cancer therapy within 2-3 weeks before starting the study. The subject has a brain tumor. Current severe, uncontrolled systemic disease. History of clinically significant heart, lung, or eye/vision problems. The subject has high blood pressure that is not well-controlled with medication. The subject has a permanent pacemaker. The subject is pregnant or breastfeeding. Positive for Hepatitis B, Hepatitis C, or HIV.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1<br>Trametinib plus Docetaxel | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: Docetaxel<br>* Chemotherapy<br>|
| Experimental: Treatment Group 2<br>Trametinib plus Erlotinib | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: Erlotinib<br>* Small molecule targeted therapy (EGFR inhibitor)<br>|
| Experimental: Treatment Group 3<br>Trametinib plus Pemetrexed | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: Pemetrexed<br>* Chemotherapy<br>|
| Experimental: Treatment Group 4<br>Trametinib plus Pemetrexed and Carboplatin | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: Pemetrexed<br>* Chemotherapy<br>Drug: Carboplatin<br>* Chemotherapy<br>|
| Experimental: Treatment Group 5<br>Trametinib plus nab-Paclitaxel | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: nab-Paclitaxel<br>* Chemotherapy<br>|
| Experimental: Treatment Group 6<br>Trametinib plus Pemetrexed and Cisplatin | Drug: Trametinib (GSK1120212)<br>* Investigational small molecule targeted therapy (MEK1/2 inhibitor)<br>Drug: Pemetrexed<br>* Chemotherapy<br>Drug: Cisplatin<br>* Chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination |  | Duration of study (approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To characterize population pharmacokinetic parameters |  | Duration of study (approximately 3 years) | 
| To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1 |  | Duration of study (approximately 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Taxotere, Cisplatin, Carboplatin, Trametinib, GSK1120212, Tarceva, KRAS, Pemetrexed, MEK inhibitor, nab-Paclitaxel, Docetaxel, Alimta, Abraxane, Erlotinib