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Metastatic MelanomaPhase 2NCT03625141

A Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases

A Phase 2 study testing Cobimetinib, Atezolizumab and Vemurafenib in people with Metastatic Melanoma, run by Hoffmann-La Roche at 22 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate the efficacy and safety of cobimetinib plus atezolizumab in participants with BRAFV600 wild-type melanoma with central nervous system (CNS) metastases and of cobimetinib plus atezolizumab and vemurafenib in BRAFV600 mutation-positive melanoma patients with CNS metastases. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Cobimetinib, Atezolizumab and Vemurafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
22 sitesin 8 countries
Study dates
13 Dec 2018to 13 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Disease-specific inclusion criteria:
  • Histologically confirmed melanoma with radiologically confirmed brain metastases
  • Documented BRAFV600 mutation status of melanoma tumour tissue using a validated genetic test.
  • Measurable brain metastases
  • Prior systemic therapy for metastatic melanoma is allowed with exceptions as detailed in the exclusion criteria
  • Prior SRT or surgical therapy of ≤ 10 brain metastases is allowed but prior WBRT is not allowed
Show all 16Show fewer
  • Adverse effects of all prior systemic or local treatment must have either returned to baseline or become stable and manageable prior to initiation of study treatment.
  • General inclusion criteria:
  • Age ≥18 years
  • Able to comply with the study protocol, in the investigator's judgment
  • ECOG Performance Status ≤ 2
  • Life expectancy of > 3 months
  • Willing and able to complete health and quality of life questionnaires required by the protocol
  • Adequate hematologic and end-organ function
  • Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least six months after completion of study therapy.
  • Male patients must agree to refrain from donating sperm for at least six months after the last dose of cobimetinib

Who cannot join

  • Disease-specific exclusion criteria:
  • Ocular melanoma
  • Leptomeningeal involvement
  • Uncontrolled tumour-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days.
  • Prior WBRT treatment for CNS disease
Show all 45Show fewer
  • Increasing corticosteroid dose during the seven days prior to initiation of study treatment or current dexamethasone or equivalent dose of > 8 mg/day
  • Prior treatment with a BRAF or MEK inhibitor
  • For patients assigned to Cohort 1 only: prior immunotherapy in the metastatic setting is not allowed. Prior immunotherapy is allowed in the adjuvant setting, provided it is completed ≥ 90 days prior to study treatment initiation.
  • For patients assigned to Cohort 2 only: prior immunotherapy in either the adjuvant or metastatic setting is not allowed.
  • Major surgical procedure other than for diagnosis within four weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or to any formulation component of cobimetinib or atezolizumab or, for patients assigned to Cohort 2 only, vemurafenib
  • Any anti-cancer therapy, including chemotherapy, hormonal therapy and radiotherapy, within two weeks prior to initiation of study treatment
  • Patients assigned to Cohort 2 only: Concomitant treatment with anticonvulsants other than gabapentin, vigabatrin and levetiracetam
  • Patients assigned to Cohort 2 only: acetaminophen is prohibited within seven days prior to initiation of study treatment unless the patient has an absolute contraindication to the to the use of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin
  • Active malignancy (other than melanoma) or a prior malignancy within the past three years
  • General exclusion criteria:
  • Known risk factors for ocular toxicity
  • History of clinically significant cardiac dysfunction
  • Inability to swallow medications
  • Malabsorption condition that would alter the absorption of orally administered medications
  • Traumatic injury within two weeks prior to initiation of study treatment
  • Prior allogeneic stem cell or solid organ transplantation
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Uncontrolled diabetes or symptomatic hyperglycaemia
  • Any Grade ≥ 3 haemorrhage or bleeding event within 28 days of study treatment initiation
  • History of stroke, reversible ischemic neurological defect, or transient ischemic attack within six months prior to study treatment initiation
  • Positive human immunodeficiency virus (HIV) test at screening
  • Hepatitis B virus (HBV) infection (chronic or acute)
  • Active hepatitis C virus (HCV) infection
  • Active tuberculosis
  • History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Severe infection within four weeks prior to initiation of study treatment
  • Signs or symptoms of infection within two weeks prior to initiation of study treatment
  • Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in, and completion of, the study
  • Any psychological, familial, sociological, or geographical condition that may hamper compliance with the protocol and follow-up after treatment discontinuation
  • Pregnancy, breastfeeding, or intention of becoming pregnant during the study. Women of childbearing potential must have a negative serum pregnancy test result within seven days prior to initiation of study treatment.
  • Treatment with therapeutic oral or IV antibiotics within two weeks prior to initiation of study treatment
  • Administration of a live, attenuated vaccine within four weeks prior to initiationof study treatment or anticipation of need for such a vaccine during the study
  • Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug, whichever is shorter, prior to study treatment initiation
  • Treatment with systemic immunosuppressive medications within two weeks prior to study treatment initiation
  • Treatment with investigational drug within 28 days or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
  • For patients to be assigned to Cohort 2 only: anticipated use of any concomitant medication during or within seven days prior to initiation of study treatment that is known to cause QT prolongation
  • Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least seven days prior to initiation of study treatment.

Trial locations and contacts

22 sites in 8 countries.

22 sites in 8 countries

Italy6 sites

  • IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

    Genoa, Liguria, 16132

  • Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

    Milan, Lombardy, 20141

  • IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B

    Naples, Campania, 80131

  • IOV - Istituto Oncologico Veneto IRCCS

    Padova, Veneto, 35128

  • Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

    Pisa, Tuscany, 56126

  • Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica

    Rome, Lazio, 00167

Other trials in Italy

Spain6 sites

  • Hospital Clínic i Provincial; Servicio de Hematología y Oncología

    Barcelona, 08036

  • Institut Catala d Oncologia Hospital Duran i Reynals

    Barcelona, 08908

  • Onkologikoa - Instituto Oncológico de Donostia

    Donostia / San Sebastian, Guipuzcoa, 20014

  • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

    Madrid, 28007

  • Hospital Universitario Virgen Macarena; Servicio de Oncologia

    Seville, 41009

  • Hospital General Universitario de Valencia; Servicio de oncologia

    Valencia, 46014

Other trials in Spain

Brazil3 sites

  • Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

    Ijuí, Rio Grande do Sul, 98700-000

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Instituto Nacional de Cancer - INCa; Oncologia

    Rio de Janeiro, Rio de Janeiro, 20560-120

Other trials in Brazil

France3 sites

  • CHU de Nantes; Cancéro-dermatologie

    Nantes, 44093

  • Institut Claudius Regaud; Departement Oncologie Medicale

    Toulouse, 31059

  • Institut Gustave Roussy; Dermatologie

    Villejuif, 94805

Other trials in France

Germany1 site

  • Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik fur Dermatologie

    Dresden, 01307

Other trials in Germany

Hungary1 site

  • Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly

    Budapest, 1122

Other trials in Hungary

Latvia1 site

  • Riga East Clinical University Hospital Latvian Oncology Centre

    Riga, LV-1079

Other trials in Latvia

Switzerland1 site

  • Universitätsspital Zürich; USZ Flughafen / H13-7-609

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: A Phase II Two Cohort Study Evaluating the Safety and Efficacy of Cobimetinib Plus Atezolizumab in BRAFV600 Wild-type Melanoma With Central Nervous System Metastases and Cobimetinib Plus Atezolizumab and Vemurafenib in BRAFV600 Mutation-positive Melanoma With Central Nervous System Metastases

This study will evaluate the efficacy and safety of cobimetinib plus atezolizumab in participants with BRAFV600 wild-type melanoma with central nervous system (CNS) metastases and of cobimetinib plus atezolizumab and vemurafenib in BRAFV600 mutation-positive melanoma patients with CNS metastases.

Being tested
Cobimetinib, Atezolizumab, Vemurafenib
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobimetinibDrug

    Also called Cotellic

    60 mg (three tablets of 20 mg each) orally (PO) once a day (QD) on Days 1-21 of each 28-day cycle.

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

    Only for cohort 2, no dose of atezolizumab will be given during the run-in period (cycle 1).

  • VemurafenibDrug

    Also called Zelboraf

    Participants will receive vemurafenib 960 mg (four 240 mg tablets) orally (PO) twice daily (BID) on days 1-21 of the run-in period (cycle 1); thereafter, they will receive vemurafenib 720 mg dose (three 240 mg tablets) PO BID on days 22-28 of cycle 1 and on days 1-28 of all subsequent cycles.

Study groups in NCT03625141
Study groupRoleWhat they receive
Cohort 1- cobimetinib and atezolizumabExperimentalParticipants with BRAFV600 wild-type disease will be administered cobimetinib on Days 1-21 of each 28-day cycle; and atezolizumab on Days 1 and 15 of each treatment cycle.
Receives: Drug: Cobimetinib; Drug: Atezolizumab
Cohort 2 - cobimetinib, atezolizumab and vemurafenibExperimentalParticipants with BRAFV600 mutation-positive disease will be administered cobimetinib, atezolizumab and vemurafenib in 28-day treatment cycles. Treatment includes a 28-day run-in period where participants will receive cobimetinib and vemurafenib only. Upon completion of the 28-day run-in period, atezolizumab will be added to their treatment regimen.
Receives: Drug: Cobimetinib; Drug: Atezolizumab; Drug: Vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intracranial Objective Response Rate (ORR)

    Intracranial ORR is defined as the percentage of participants with either a complete response (CR) or a partial response (PR) in their intracranial disease based on two consecutive assessments >= 4 weeks apart. Disease status for this endpoint will be determined by an Independent Review Committee (IRC) in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) with modified measurability definition for intracranial lesions (>= 0.5 cm by MRI) and allowing up to five intracranial target lesions. CR is defined as disappearance of all lesions. PR is defined as >=30% decrease in tumor burden, in the absence of CR. The primary endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.

    Measured: Baseline up to cut of date (approximately 2.5 years)

Secondary outcomes (10)

  1. Extracranial ORR

    Extracranial ORR, defined as the percentage of participants with either a CR or PR in their extracranial disease based on two consecutive assessments >=4 weeks apart, as determined by the investigator according to RECIST v1.1.

    Measured: Baseline up to cut of date (approximately 2.5 years)

  2. Overall ORR

    Overall ORR, defined as the percentage of participants with either a CR or PR in their overall disease (i.e. including intracranial and extracranial disease) based on two consecutive assessments >= 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

    Measured: Baseline up to cut of date (approximately 2.5 years)

  3. Progression-Free Survival (PFS)

    Intracranial, extracranial and overall PFS defined as the time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1.

    Measured: Baseline up to cut of date (approximately 2.5 years)

  4. Duration of Response (DOR)

    Intracranial, extracranial and overall DOR, defined as the time from the first occurrence of a documented objective response based on two consecutive assessments ≥ 4 weeks apart to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.

    Measured: Baseline up to cut of date (approximately 2.5 years)

  5. Disease Control Rate (DCR)

    Intracranial, extracranial and overall DCR, defined as the percentage of participants with a CR or PR or stable disease (SD) at 16 weeks from study treatment initiation, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. PR was defined as at least a 30 percent (%) decrease in sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression is defined as >=20% increase in tumor burden. This endpoint is analyzed on the BRAFV600 mutation positive (Cohort 2) only as the Sponsor had discontinued enrolment into Cohort 1. Data for Cohort 1 was not collected nor analyzed for this outcome measure.

    Measured: At 16 weeks

  6. Overall Survival (OS)

    OS is defined as the time from study treatment initiation to death from any cause.

    Measured: Baseline up to 4 years, 4 months

  7. Time to Cognitive Symptom Deterioration

    Time from study treatment initiation to cognitive symptom deterioration, defined as a change (>= 10 points on a 0-100 scale) on selected scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BN20) (visual disorder, motor dysfunction, communication deficit, headaches, seizures and drowsiness).

    Measured: Up to 48 months

  8. Time to Symptom and Function Deterioration

    Time from study treatment initiation to symptom and function deterioration defined as a change (>= 10 points on a 0-100 scale) in fatigue, physical functioning, cognitive functioning, or role functioning as measured by the Fatigue, Physical, Cognitive, Role Functioning scales of the EORTC QLQ-C30.

    Measured: Up to 48 months

  9. Duration of Stable/Improved Health-related Quality of Life (HRQoL) Scores

    Duration of Stable/Improved HRQoL scores as assessed through use of the two-item Global Health Status (GHS)/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30.

    Measured: Baseline up to cut of date (approximately 2.5 years)

  10. Percentage of Participants With Adverse Events

    The safety profile of Cobimetinib plus Atezolizumab and Cobimetinib plus Atezolizumab plus Vemurafenib is evaluated in terms of occurrence and severity of AEs. Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)

    Measured: Baseline up to 4 years, 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2018
  2. Study start13 Dec 2018
  3. Primary completion7 Jun 2021
  4. Study completion13 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03625141
Sponsor's protocol ID
MO39136
Other IDs
2018-000759-41, 2018
Status last verified
Apr 2024
First submitted
2 Aug 2018
Last updated
11 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Dummer R, Queirolo P, Gerard Duhard P, Hu Y, Wang D, de Azevedo SJ, Robert C, Ascierto PA, Chiarion-Sileni V, Pronzato P, Spagnolo F, Mujika Eizmendi K, Liszkay G, de la Cruz Merino L, Tawbi H. Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2023 Dec;24(12):e461-e471. doi: 10.1016/S1470-2045(23)00334-0. Epub 2023 Jul 14.

    PubMed 37459873

  • Dummer R, Queirolo P, Abajo Guijarro AM, Hu Y, Wang D, de Azevedo SJ, Robert C, Ascierto PA, Chiarion-Sileni V, Pronzato P, Spagnolo F, Mujika Eizmendi K, Liszkay G, de la Cruz Merino L, Tawbi H. Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2022 Sep;23(9):1145-1155. doi: 10.1016/S1470-2045(22)00452-1. Epub 2022 Aug 5.

    PubMed 35940183

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cobimetinib, Atezolizumab and Vemurafenib in people with Metastatic Melanoma, run by Hoffmann-La Roche at 22 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy, Spain, Brazil, France, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intracranial Objective Response Rate (ORR) (time frame: Baseline up to cut of date (approximately 2.5 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03625141, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2024.

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