ClinicalTrials.gov record NCT05768178

DETERMINE Trial Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 05: Vemurafenib in Combination With Cobimetinib in Adult Patients With BRAF Positive Cancers.

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2/3A study that tests whether a treatment works while continuing to check safety, in a larger group than a phase 2 study alone. It combines the aims of phase 2 and phase 3 in one protocol.
Age18 years old and older
SexAll
LocationUnited Kingdom
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This treatment arm tests the combination of two oral cancer drugs, vemurafenib and cobimetinib, in adults whose tumours have a BRAF V600 mutation. Participants receive the drugs in repeated 28-day cycles while the study collects biopsies, blood samples, imaging, and quality-of-life questionnaires; treatment continues until progression, unacceptable side effects, or withdrawal. The arm is part of the DETERMINE platform and aims to generate evidence that could inform NHS/Cancer Drugs Fund access decisions.

What it is studying. The study is evaluating the effect of giving vemurafenib together with cobimetinib to adults whose cancers carry a BRAF V600 mutation. It will measure tumour response and how long any benefit lasts, plus safety and quality-of-life outcomes.

What the researchers hope to learn. Scientific goals are to measure objective tumour response and durable clinical benefit (including at 24 weeks), duration of response, progression-free and overall survival, safety (including serious and high-grade adverse events), and quality of life. The arm also aims to produce evidence that could be used to seek routine access through the NHS and the Cancer Drugs Fund if results support that step.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

This clinical trial is looking at a combination of drugs called vemurafenib and cobimetinib. Vemurafenib is approved as standard of care for adult patients with unresectable or metastatic melanoma. Cobimetinib is approved as standard of care in combination with vemurafenib for the treatment of adult patients with unresectable or metastatic melanoma. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Cobimetinib and vemurafenib work in patients with these types of cancers which have certain changes in the cancer cells called BRAF V600 mutation-positive. Investigators now wish to find out if it will be useful in treating patients with other cancer types which are also BRAF V600 mutation-positive. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Vemurafenib
  • Cobimetinib

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 05 (VEMURAFENIB AND COBIMETINIB) OUTLINED BELOW*
  • *When vemurafenib and cobimetinib-specific inclusion/

Exclusion criteria

  • or precautions below differ from those specified in the Master Protocol, the vemurafenib and cobimetinib-specific criteria will take precedence.
  • A. Confirmed diagnosis of a malignancy harbouring any actionable BRAF V600 mutation using an analytically validated next-generation sequencing method.
  • B. Adult patients ≥18 years old.
  • C. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken.
  • D. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility.
  • E. Women of childbearing potential are eligible provided that they meet the following criteria:
  • Have a negative serum or urine pregnancy test before enrolment and;
  • Agree to sexual abstinence OR to use any two forms of highly effective or effective methods together (at least one to be non-hormonal) such as:
  • Highly effective methods:
  • combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system (IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • Effective methods:
  • progestogen-only oral hormonal contraception not associated with inhibition of ovulation
  • male or female condom with or without spermicide
  • cap, diaphragm or sponge with spermicide
  • Effective from the first administration of vemurafenib or cobimetinib (whichever is first), throughout the trial and for six months after the last administration of vemurafenib or cobimetinib (whichever is later).
  • F. Male patients with partners who are women of childbearing potential, are eligible provided that they agree to the following, from the first administration of vemurafenib or cobimetinib (whichever is first), throughout the trial and for six months after the last administration of vemurafenib or cobimetinib (whichever is later):
  • Agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide) or to sexual abstinence
  • Non-vasectomised male patients with partners who are women of childbearing potential must also be willing to ensure that their partner uses a highly effective method of contraception as in E, above.
  • Male patients with pregnant or lactating partners must be advised to use barrier method contraception (e.g. condom) to prevent drug exposure of the foetus or neonate.
  • All male patients must refrain from donating sperm for the same period.
  • A. Diagnosis of unresectable or metastatic melanoma with a BRAF V600 mutation.
  • B. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for six months following their last dose of vemurafenib or cobimetinib, whichever is later.
  • C. Patients with QTcF (Corrected QT interval by Fridericia) at screening of >450 ms for males and >470 ms for females measured on triplicate ECG (if 1/3 readings show >450/470 ms then patient is ineligible).
  • D. Patients with any history of long QT syndrome or Torsades de Pointes (or any concurrent medication with a known risk of inducing Torsades de Pointes).
  • E. Known hypersensitivity to vemurafenib or cobimetinib or any of the excipients.
  • F. Patients unable to swallow vemurafenib and cobimetinib intact, without chewing or crushing the tablets (as per the dosing schedule).
  • G. Patients who were administered a live, attenuated vaccine within 28 days prior to enrolment, or anticipation of need for such a vaccine during vemurafenib and cobimetinib treatment or within six months after the final dose of vemurafenib and cobimetinib.
  • H. Patients with clinically significant pre-existing cardiac conditions including (within the last three months prior to screening):
  • Uncontrolled or symptomatic angina,
  • Uncontrolled atrial or ventricular arrhythmias,
  • Class III \& IV New York Heart Association congestive heart failure,
  • Left ventricular ejection fraction (LVEF) <50%,
  • Myocardial infarction
  • I. Ophthalmological disorders: History of retinal detachment, severe visual impairment, central serous chorioretinopathy, neovascular retinopathy, or retinopathy of prematurity.
  • Patients with low grade gliomas causing visual impairment may be considered eligible and monitored with close ophthalmological monitoring.
  • J. History of pancreatitis.
  • K. History of central nervous system (CNS) or gastrointestinal (GI) haemorrhage within three months of trial entry.
  • L. Patients with any history of haemorrhagic stroke.
  • M. Prior treatment with the same class of drug unless presence of a resistance alteration known to be potentially sensitive to either vemurafenib or cobimetinib. Prior sorafenib use is permissible following a washout period of 10 days.
  • N. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial or absorption of oral medications that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.
  • O. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of vemurafenib and cobimetinib, including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided the each of the following conditions are met:
  • CD4 count ≥350/μL;
  • undetectable viral load;
  • receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and
  • no HIV/ acquired immune deficiency syndrome-associated opportunistic infection in the last 12 months.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

DETERMINE Treatment Arm 05 (vemurafenib and cobimetinib) aims to evaluate the efficacy of vemurafenib and cobimetinib in adult patients with rare* cancers with BRAF V600 mutations or in common cancers where BRAF V600 mutations are considered to be infrequent. *Rare is defined generally as incidence less than 6 cases in 100,000 patients or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts. Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes. Treatment: Patients will receive vemurafenib and cobimetinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT). After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After molecular review, consenting participants provide baseline tissue and blood samples (or bone marrow/lymph node samples for blood cancers). They take oral vemurafenib (960 mg twice daily) continuously and cobimetinib (60 mg once daily, days 1–21 of each 28‑day cycle) until disease progression, unacceptable side effects, or withdrawal. During treatment participants give blood samples at intervals, complete quality‑of‑life questionnaires each cycle, and have disease assessments (imaging) every 2 cycles (with later spacing possible). After stopping study treatment they are followed up every 3 months for up to 2 years.

How the study is structured. Interventional (Phase 2/3) treatment study, non-randomized and open-label with a single treatment group. Adult participants receive oral vemurafenib twice daily and oral cobimetinib once daily for 21 of each 28 days, continuing until disease progression, unacceptable adverse events, or withdrawal of consent. The study includes a baseline biopsy and blood samples for research, on-treatment blood draws, regular imaging and disease assessments (every 2 cycles initially), and quality-of-life questionnaires; patients are followed every 3 months for up to 2 years after treatment.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United Kingdom. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Erdheim-Chester disease

Clinical trials11 trials listed for Erdheim-Chester diseaseEvery trial the registry lists for Erdheim-Chester disease, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Erdheim-Chester disease researchLatest monthly update: September 2026. Includes: BRAF-targeted treatment. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Mar 1, 2023
Primary completion
October 2029 (estimated)
Study completion
October 2029 (estimated)
Target enrollment
30 participants (estimated)
Last updated on registry
Nov 24, 2025
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Cancer Research UK
Collaborators
  • University of Manchester
  • University of Birmingham
  • Royal Marsden NHS Foundation Trust
  • Hoffmann-La Roche

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (16)

Terms used on this page · explanations by MedicalUpdates.ai

standard of care
Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
ELIGIBILITY CRITERIA
The rules the study team uses to decide who may take part. They are usually split into inclusion criteria and exclusion criteria.
TREATMENT ARM
One of the groups in a study. Each arm receives a particular intervention, comparator or no intervention, so the groups can be compared.
biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
baseline
Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
Women of childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
enrolment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
QTcF
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
at screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
Prior treatment
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
washout period
A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
exclusion criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
adverse events
Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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