Uprosertib + Dabrafenib + Trametinib for Advanced Skin Cancer

Recruiting at 16 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, CYP2C8 inducers

Disqualifiers: Cardiac arrhythmias, Diabetes, Hypertension, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II trial studies the side effects and the best dose of uprosertib when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Uprosertib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving uprosertib with dabrafenib and trametinib may be a better treatment for cancer.

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

Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

I can provide tissue from when my disease worsened after BRAF inhibitor therapy or allow a new biopsy.

Patients must have specific results for their lab tests.

See 17 more

Exclusion Criteria

Patients must not be pregnant or nursing

I don't have any serious ongoing illnesses, recent major surgery, or history of severe lung disease.

I do not have a history or current signs of retinal vein occlusion.

See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive dabrafenib, trametinib, and uprosertib in cycles of 28 days, with dose escalation to determine the maximum-tolerated dose

Up to 56 days for dose escalation, then 28-day cycles

Every 2 weeks during days 1-56, then every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 3 months for 1 year, then every 6 months for 2 years

What Are the Treatments Tested in This Trial?

Interventions

Dabrafenib
Trametinib
Uprosertib

Trial Overview The trial is testing the combination of uprosertib with dabrafenib and trametinib in patients with advanced cancer stages. It aims to find the best dose that can block enzymes needed for tumor cell growth and determine how effective this drug combo is compared to current treatments.

How Is the Trial Designed?

1Treatment groups

Experimental Treatment

Group I: Treatment (uprosertib, dabrafenib, trametinib)Experimental Treatment7 Interventions

Dabrafenib mesylate and uprosertib (Phase I): Patients receive dabrafenib PO BID and uprosertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, MRI, and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial. Dabrafenib mesylate, trametinib dimethyl sulfoxide, and uprosertib (Phase I and Phase II): Patients receive dabrafenib PO BID, trametinib PO QD, and uprosertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, MRI, and blood sample collection throughout trial. Patients may also undergo a biopsy throughout the trial.

Dabrafenib is already approved in European Union, United States, Canada, Japan for the following indications: