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
Overview
- Phase
- Phase 1
- Intervention
- Trametinib (GSK1120212)
- Conditions
- Cancer
- Sponsor
- GlaxoSmithKline
- Enrollment
- 169
- Locations
- 1
- Primary Endpoint
- To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
Treatment Group 1
Trametinib plus Docetaxel
Intervention: Trametinib (GSK1120212)
Treatment Group 1
Trametinib plus Docetaxel
Intervention: Docetaxel
Treatment Group 2
Trametinib plus Erlotinib
Intervention: Trametinib (GSK1120212)
Treatment Group 2
Trametinib plus Erlotinib
Intervention: Erlotinib
Treatment Group 3
Trametinib plus Pemetrexed
Intervention: Trametinib (GSK1120212)
Treatment Group 3
Trametinib plus Pemetrexed
Intervention: Pemetrexed
Treatment Group 4
Trametinib plus Pemetrexed and Carboplatin
Intervention: Trametinib (GSK1120212)
Treatment Group 4
Trametinib plus Pemetrexed and Carboplatin
Intervention: Pemetrexed
Treatment Group 4
Trametinib plus Pemetrexed and Carboplatin
Intervention: Carboplatin
Treatment Group 5
Trametinib plus nab-Paclitaxel
Intervention: Trametinib (GSK1120212)
Treatment Group 5
Trametinib plus nab-Paclitaxel
Intervention: nab-Paclitaxel
Treatment Group 6
Trametinib plus Pemetrexed and Cisplatin
Intervention: Trametinib (GSK1120212)
Treatment Group 6
Trametinib plus Pemetrexed and Cisplatin
Intervention: Pemetrexed
Treatment Group 6
Trametinib plus Pemetrexed and Cisplatin
Intervention: Cisplatin
Outcomes
Primary Outcomes
To determine the safety, tolerability, and recommended phase II dosing regimen of each GSK1120212-based treatment combination
Time Frame: Duration of study (approximately 3 years)
Secondary Outcomes
- To evaluate the anti-tumor activity as assessed by tumor response rate according to RECIST v1.1(Duration of study (approximately 3 years))
- To characterize population pharmacokinetic parameters(Duration of study (approximately 3 years))