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Protein Kinase Inhibitor

Uprosertib + Dabrafenib + Trametinib for Advanced Skin Cancer

Phase 1 & 2

Waitlist Available

Led By Antoni Ribas

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have locally advanced unresectable stage IIIC or metastatic stage IV cancer with either progression to prior therapy or a newly diagnosed cancer that does not have an available treatment with curative intent

Patients must have Zubrod performance status =< 1

Must not have

Patients must not be receiving specific medications or substances

Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib or other agents used in this study including dimethyl sulfoxide (DMSO)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up disease assessments every 8 weeks for up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the effects and best dose of uprosertib when given with dabrafenib and trametinib for stage IIIC-IV cancer.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include but are not limited to: changes in heartbeat rhythm, high blood pressure, bleeding risks including internal bleeding, inflammation of lungs (pneumonitis), liver function changes due to hepatitis infection risk increase, vision problems such as retinal vein occlusion (RVO), and possible allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is advanced and cannot be surgically removed, or it has spread, and previous treatments didn’t work.

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I am fully active and can carry on all pre-disease activities without restriction.

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I can swallow pills and don't have major stomach issues affecting medicine absorption.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not currently taking any excluded medications.

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I have no allergies to dabrafenib or similar drugs, including DMSO.

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

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My blood pressure is under control.

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I do not have an active hepatitis B or C infection.

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I do not have a history of heart conditions or recent heart events.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ disease assessments every 8 weeks for up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~disease assessments every 8 weeks for up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and disease assessments every 8 weeks for up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib and Trametinib.

Maximum-tolerated Dose (MTD) of Akt Inhibitor GSK2141795 in Combination With Dabrafenib.

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial Responses) as Assessed by RECIST Version 1.1 of the Doublet Regimen GSK2141795 + Dabrafenib at the Phase I Determined MTD. (Phase II)

+1 more

Secondary study objectives

Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Doublet Regimen

Overall Survival (Phase II) of Patients Treated at the Phase I Determined MTD of Triplet Regimen

Progression-free Survival as Assessed by RECIST Version 1.1 of the Doublet Regimen at the Phase I Determined MTD (Phase II)

+1 more

Other study objectives

Prevalence of Markers

Side effects data

From 2018 Phase 2 trial • 9 Patients • NCT02281760

100%

Chills

100%

Rash

100%

Hyperthermia

100%

Anaemia

83%

Dehydration

67%

Blood urea increased

67%

Fatigue

67%

Headache

67%

Lipase increased

50%

Back pain

50%

Nausea

50%

Diarrhoea

50%

Amylase increased

50%

Blood creatine phosphokinase increased

50%

Hyponatraemia

50%

Blood cholesterol increased

50%

Pain in extremity

50%

Blood creatinine increased

33%

Red blood cells urine

33%

Hypertriglyceridaemia

33%

Alanine aminotransferase increased

33%

Blood alkaline phosphatase increased

33%

Blood pressure increased

33%

Hypertension

33%

Disturbance in attention

33%

Labile hypertension

33%

Vomiting

33%

Dyspepsia

33%

Urinary tract infection

33%

Aspartate aminotransferase increased

33%

Myalgia

33%

Cough

33%

Hypotension

33%

Ataxia

33%

Malaise

33%

Abdominal pain

17%

Hypomagnesaemia

17%

Arthritis

17%

Viral infection

17%

Hypernatraemia

17%

Anorexia nervosa

17%

Nasal congestion

17%

Gamma-glutamyltransferase increased

17%

Pharyngitis

17%

Sweating fever

17%

Erythema nodosum

17%

Gingival recession

17%

Confusional state

17%

Cystatin C increased

17%

Syncope

17%

Lip dry

17%

Blood thyroid stimulating hormone decreased

17%

Prothrombin time prolonged

17%

Hyperuricaemia

17%

Arthralgia

17%

Joint effusion

17%

Memory impairment

17%

Acute kidney injury

17%

Proteinuria

17%

Penile pain

17%

Urosepsis

17%

Hyperglycaemia

17%

Dyspnoea

17%

Lymphadenopathy

17%

Skin sensitisation

17%

Paronychia

17%

Leukopenia

17%

Vertigo

100%

80%

60%

40%

20%

Study treatment Arm

Combination Therapy With Dabrafenib and Trametinib in Patients With ECD

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1090

Biospecimen Collection

2004

Completed Phase 3

~2020