Uprosertib + Dabrafenib + Trametinib for Advanced Skin Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial aims to determine the best dose and assess the side effects of a new treatment combination for advanced skin cancer. It tests uprosertib (an experimental treatment) with dabrafenib and trametinib to evaluate their effectiveness in stopping cancer cell growth. The trial targets individuals with stage IIIC-IV melanoma who have a specific genetic mutation called BRAF^V600 and have not responded to other treatments. Participants should have cancer that has spread and cannot be surgically removed. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take medications that strongly affect certain liver enzymes or use herbal remedies like St. John's wort. It's best to discuss your current medications with the trial team.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of dabrafenib and trametinib can help some patients with a certain type of skin cancer live longer, and most people tolerate these drugs well. However, when uprosertib was added, past studies found that 59% of patients experienced noticeable side effects, and 6% had very serious ones, indicating that uprosertib might be harder for some patients to tolerate.
In these early studies, researchers continue to test the combination of all three drugs to determine the right dose and ensure safety. As the study is in an early phase, researchers are still learning about how these drugs work together and their effects on patients.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of uprosertib, dabrafenib, and trametinib for advanced skin cancer because it targets the cancer cells in a unique way. While standard treatments often focus on blocking a single pathway, this combination targets multiple pathways involved in cancer cell growth and survival. Uprosertib is a new addition that inhibits a protein called AKT, which is crucial for cancer cell metabolism and survival, potentially enhancing the effectiveness of dabrafenib and trametinib. This multi-targeted approach holds the promise of being more effective in halting disease progression compared to existing treatments.
What evidence suggests that this trial's treatments could be effective for advanced skin cancer?
Studies have shown that using dabrafenib and trametinib together can slow advanced skin cancer, with about 19% of patients experiencing no cancer progression after five years. In this trial, participants will receive a combination of uprosertib, dabrafenib, and trametinib. Adding uprosertib to these drugs might enhance their effectiveness by blocking enzymes that help cancer grow. Research indicates that trametinib increases dabrafenib levels in the body, potentially making the treatment more effective. This combination targets several pathways of cancer cell growth, potentially offering a stronger treatment option.23678
Who Is on the Research Team?
Antoni Ribas
Principal Investigator
SWOG Cancer Research Network
Are You a Good Fit for This Trial?
This trial is for adults with stage IIIC-IV cancer, specifically those with BRAF^V600 mutant metastatic cancer. Participants must have resolved any previous treatment side effects to a mild level and be able to take oral medication without significant gastrointestinal issues. They should not be pregnant or nursing, have active hepatitis B/C, uncontrolled illnesses like heart disease or diabetes, or a history of severe allergic reactions to similar drugs.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Patients receive dabrafenib, trametinib, and uprosertib in cycles of 28 days, with dose escalation to determine the maximum-tolerated dose
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Dabrafenib
- Trametinib
- Uprosertib
Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications:
- Unresectable or metastatic melanoma with a BRAF V600 mutation
- Adjuvant treatment of melanoma with a BRAF V600 mutation
- Unresectable or metastatic melanoma with a BRAF V600E mutation
- Adjuvant treatment of melanoma with a BRAF V600E or V600K mutation
- Metastatic non-small cell lung cancer with a BRAF V600E mutation
- Unresectable or metastatic melanoma with a BRAF V600 mutation
- Adjuvant treatment of melanoma with a BRAF V600 mutation
- Unresectable or metastatic melanoma with a BRAF V600 mutation
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor
GlaxoSmithKline
Industry Sponsor
Dame Emma Walmsley
GlaxoSmithKline
Chief Executive Officer since 2017
MA in Classics and Modern Languages from Oxford University
Dr. Hal Barron
GlaxoSmithKline
Chief Medical Officer since 2018
MD from Harvard Medical School
Novartis Pharmaceuticals
Industry Sponsor
Dr. Vas Narasimhan
Novartis Pharmaceuticals
Chief Executive Officer since 2018
MD from Harvard Medical School
Dr. Shreeram Aradhye
Novartis Pharmaceuticals
Chief Medical Officer since 2021
MD