Malignant MelanomaPhase 2CONVERCENCT02537600
Vemurafenib and Cobimetinib Combination in BRAF Mutated Melanoma With Brain Metastasis
A Phase 2 study testing Cobimetinib + Vemurafenib combination treatment in people with Malignant Melanoma, run by Center Eugene Marquis at 17 sites in France.
Trial summary
The purpose of this study is to determine wether cobimetinib + vemurafenib combination treatment is effective in the treatment of BRAFV600-mutated melanoma patients with brain metastasis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Cobimetinib + Vemurafenib combination treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 17 sitesFrance
- Study dates
- Dec 2015to 6 Nov 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Men and women ≥ 18 years of age.
- Histologically confirmed metastatic cutaneous melanoma, mucous melanoma, or melanoma of unknown primary origin (stage IV).
- Documented BRAFV600 mutation determined in a hospital center specializing in the molecular genetics of cancer that is certified by the French national cancer institute (INCa).
- Presence of Brain Metastases (BM) for which surgical resection is not a reasonable treatment option but that may be amenable to treatment with targeted therapy, to be decided in the onco-dermatology and/or neuro-oncology multidisciplinary team meeting (MDTM).
- At least one measurable BM in at least one dimension between 5 and 40 mm on magnetic resonance imaging (MRI) with gadolinium (modified RECIST 1.1).
- Patients having previously received a maximum of two systemic therapies during the metastatic phase, except BRAF, Map ERK Kinase (MEK) or Extracellular signal Regulated Kinase (ERK) inhibitors or tyrosine kinase pan-inhibitors (TKIs); prior ipilimumab therapy is allowed if patients have documented cerebral progression 12 weeks after the last injection of treatment and if MRI confirms progression at least 4 weeks later. A period of at least 6 weeks must be observed between the last dose of ipilimumab and the first administration of the study treatments. Prior treatment with anti-programmed cell death (PD)-1 or anti-PD ligand 1 (PD-L1) is allowed.
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- For patients who have received prior whole brain radiotherapy or radiosurgery and/or surgery for BM (cohorts B and C) demonstration of a significant progression of at least one lesion according to RECIST 1.1 criteria, . after at least 4 weeks have elapsed since this treatment has ended, and MRI at inclusion must demonstrate a significant progression of at least one lesion according to RECIST 1.1 criteria.
- Patients with symptomatic or asymptomatic BM.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Patients must have recovered from all the side effects (grade ≤ 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-Common Toxicity Criteria for Adverse Event (CTCAE), version 4.03) of their most recent systemic or local treatment (except alopecia).
- Signed and dated informed consent before carrying out any procedures that are specific to the trial and are not procedures (examinations) conducted as part of normal patient care.
- Patients willing and able to comply with scheduled visits, treatment schedule, laboratory testing and other trial procedures.
- Negative serum pregnancy test within 10 days of the first dose of the study treatment for women of childbearing age. Women of non-childbearing potential may be included if they are surgically sterile or postmenopausal for ≥ 1 year.
- Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after the last administration of the study treatment. Effective methods of contraception are defined as those that have a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as injectable implants combined with oral contraception or intra-uterine devices, or as total abstinence in cases where the lifestyle of the patient ensures compliance.
- Adequate hematologic, renal and hepatic function within 14 days of the administration of treatment:
- Hematologic Leucocytes > 2.0 x 109/L Neutrophils > 1.0 x 109/L Hemoglobin (transfusion allowed) > 9 g/dL Platelets > 100 x 109/L Liver Total bilirubin < 1.5 x upper limit of normal (ULN) (< 3.0 mg/dL for patients with Gilbert syndrome) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN if there is liver metastasis) Alkaline phosphatase (ALP) < 3 x ULN (< 5 x ULN if there is liver or bone metastasis) Kidney Creatinine Or creatinine clearance < 1.5 x ULN ≥ 40 mL/min (Cockcroft-Gault formula)
Who cannot join
- Uveal melanoma. Patients with mucous melanoma or melanoma of unknown primary origin are eligible if BRAFV600 mutation is confirmed.
- Symptomatic or diffuse leptomeningeal involvement.
- Symptoms of uncontrolled intracranial pressure. Increasing corticosteroid dose during the 7 days prior to the first dose of the study treatment is an exclusion criterion. Patients receiving corticosteroids and patients presenting intermittent seizures may be enrolled if the dose of corticosteroids and anti-epileptic treatments has been stable for at least 2 weeks before inclusion.
- Indication for urgent neurosurgery or radiotherapy.
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been treated to complete remission or untreated stage I chronic lymphoid leukemia.
- Known human immunodeficiency virus (HIV) infection.
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- Prior treatment with BRAF, MEK, or ERK inhibitors or pan-TKIs.
- Concurrent administration of any anticancer therapies other than those administered in this study.
- Treatment with any cytotoxic and/or investigational drug or targeted therapy within 4 weeks of the first dose of the study treatment, or ipilimumab, anti-PD-1 or anti-PD-L1 immunotherapy within 8 weeks of the study treatment and/or radiation therapy within 2 weeks of the study treatment.
- Pregnant or breastfeeding women.
- Refractory nausea and vomiting, intestinal malabsorption, or significant bowel resection that would preclude adequate absorption or cause an inability to swallow tablets.
- Ulcerative colitis, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticula or other gastrointestinal condition increasing the risk of perforation.
- Any of the following within the 6 months prior to the first dose of study treatment:
- myocardial infarction,
- severe/unstable angina,
- symptomatic congestive heart failure (New York Heart Association grade ≥2),
- cerebrovascular accident or transient ischemic attack,
- pulmonary embolism,
- grade > 2 hypertension not controlled by medications.
- History or presence of clinically significant ventricular or atrial arrhythmia ≥ grade 2 (NCI-CTCAE Version 4.03).
- Corrected QT (cQT) interval ≥ 450 ms and left ventricular ejection fraction (LVEF) below the lower limit of normal (LLN) or < 50% (scintigraphy or ultrasound).
- History, risk factor or retinal pathology that increases the risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): evidence of retinal pathology that is considered a risk factor for RVO or CSR, or a history of retinal detachment, central serous chorioretinopathy or retinal vein thrombosis. The risk factors for RVO are listed below:
- Uncontrolled glaucoma with intraocular pressures > 21 mm Hg,
- Serum cholesterol ≥ Grade 2 (≥ 7.75 mmol/L),
- Hypertriglyceridemia ≥ Grade 2 (≥ 3.42 mmol/L),
- Hyperglycemia (fasting) ≥ Grade 2 (≥ 8.9 mmol/L).
- Serious or uncontrolled medical disorders that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to follow the protocol, or interfere with the interpretation of study results.
- Patients Under guardianship or curators, maintenance of justice, non-informed about diagnosis, unable to follow study medical requirement for geographical, social or psychic reasons.
- Patients with abnormal blood electrolyte test (Ca, Mg, K and Na) that could not be corrected.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
CHU de Bordeaux
Bordeaux, 33000
CHU Ambroise Paré
Boulogne, 92104
CHU Brest - Hôpital Morvan
Brest
CHU Caen - Hôpital Clémenceau
Caen, 14033
Hôpital Henri Mondor
Créteil, 94010
CHU de Dijon
Dijon
CHU Albert Michallon
Grenoble, 38014
Centre Hospitalier du Mans
Le Mans, 72037
CHRU Lille
Lille, 59037
Centre Hospitalier Lyon Sud
Lyon, 69495
CHU de Nantes
Nantes, 44093
Groupe Hospitalier l'Archet
Nice, 06202
Hôîtal St louis
Paris, 75010
Hôpital Cochin
Paris, 75014
Hôpital Bichat
Paris, 75018
Centre Eugène Marquis
Rennes, 35042
CHU Tours
Tours, 37044
About this study
Official title: Evaluation of Cobimetinib + Vemurafenib Combination Treatment in Patients With Brain Metastasis BRAFV600 Mutated Cutaneous Melanoma
The purpose of this study is to determine wether cobimetinib + vemurafenib combination treatment is effective in the treatment of BRAFV600-mutated melanoma patients with brain metastasis
Read the detailed description
Patients will be enrolled into 3 cohorts:
- Cohort A : Neurologically asymptomatic patients who have not received prior local treatment ;
- Cohort B. Neurologically asymptomatic patients who have received prior local treatment;
- Cohort C. Neurologically symptomatic patients who have or have not received prior local treatment Every patients will be treated with Vemurafenib 960 mg PO, twice daily from D1 to D28, continuously
Cobimetinib 60 mg PO, once daily, from D1 to D21 - 1 cycle = 28 days
Treatment will be administered until progression (intracranial or extracranial), unacceptable toxicity, withdrawal of consent, death or decision of the treating investigator.
Patients who develop intracranial or extracranial progression and who, in the opinion of the treating investigator, could benefit from continuing treatment may continue treatment with vemurafenib and cobimetinib after approval from the principal investigator.
Patients who discontinue the study treatment will undergo an end-of-treatment visit 30 days after the last dose of vemurafenib and/or cobimetinib.
Patients who discontinue the study treatment for any reason other than progression (e.g. toxicity) must be followed up every 8 weeks unless they withdraw their consent.
- Conditions
- Malignant Melanoma
- Being tested
- Cobimetinib + Vemurafenib combination treatment
- Keywords
- BRAF mutation, Brain metastasis, Cobimetinib + Vemurafenib combination treatment
- Medical subject headings
- Melanoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cobimetinib + Vemurafenib combination treatmentDrug
Also called Vemurafenib = Zelboraf (commercial name), Cobimetinib = code number RO5514041/F04
Patients will be treated from day 1 to day 28 with Vemurafenib and from day 1 to day 21 with Cobimetinib. Day 1 to Day 28 corresponds to one cycle of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Cobimetinib + Vemurafenib combination | Experimental | Every patients will be treated with :
Vemurafenib 1920 mg / day from day 1 to day 28 continuously Cobimetinib 60 mg / day from day 1 to day 21 One cycle = 28 days Intervention = Cobimetinib + Vemurafenib combination treatment. Only one arm. Receives: Drug: Cobimetinib + Vemurafenib combination treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete or partial intracranial response rate in cohort A on the evaluation of each patient's best tumor response by the centralized review committee according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.
Measured: From baseline up to 36 months
Secondary outcomes (7)
Complete or partial intracranial response rates in cohorts B and C based on the evaluation of each patient's best tumor response by the centralized review committee according to modified RECIST 1.1 criteria.
Measured: Up to 36 months
Intracranial duration of response (DR) in cohorts A, B and C.
Measured: Up to 36 months
Overall response rate of cohorts A, B and C
Measured: Up to 36 months
Overall survival in cohorts A, B and C
Measured: Up to 36 months
Frequency of Adverse events
Measured: Up to 36 months
Overall duration of response (DR) in cohorts A, B and C.
Measured: Up to 36 months
Patient free survival in cohorts A, B and C
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2015 (estimated)
- Study startDec 2015
- Primary completion6 Nov 2019
- Study completion6 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center Eugene Marquis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thierry Lesimple, MD, Principal investigator, Centre Eugène Marquis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537600
- Sponsor's protocol ID
- 2013-TL-MEL-Th
- Other IDs
- 2014-001671-30, 2014
- Acronym
- CONVERCE
- Status last verified
- Jan 2019
- First submitted
- 18 Aug 2015
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Cobimetinib + Vemurafenib Combination Treatment in Patients With Brain Metastasis BRAFV600 Mutated Cutaneous Melanoma
- ClinicalTrials.gov ID
- NCT02537600
- Acronym / sponsor ID
- CONVERCE / 2013-TL-MEL-Th
- Conditions
- Malignant Melanoma
- Keywords
- BRAF mutation, Brain metastasis, Cobimetinib + Vemurafenib combination treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Center Eugene MarquisUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- 6 Nov 2019 (actual)
- Study completion
- 6 Nov 2019 (actual)
- First posted
- 1 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine wether cobimetinib + vemurafenib combination treatment is effective in the treatment of BRAFV600-mutated melanoma patients with brain metastasis
Detailed description
Patients will be enrolled into 3 cohorts:
- Cohort A : Neurologically asymptomatic patients who have not received prior local treatment ;
- Cohort B. Neurologically asymptomatic patients who have received prior local treatment;
- Cohort C. Neurologically symptomatic patients who have or have not received prior local treatment Every patients will be treated with Vemurafenib 960 mg PO, twice daily from D1 to D28, continuously
Cobimetinib 60 mg PO, once daily, from D1 to D21 - 1 cycle = 28 days
Treatment will be administered until progression (intracranial or extracranial), unacceptable toxicity, withdrawal of consent, death or decision of the treating investigator.
Patients who develop intracranial or extracranial progression and who, in the opinion of the treating investigator, could benefit from continuing treatment may continue treatment with vemurafenib and cobimetinib after approval from the principal investigator.
Patients who discontinue the study treatment will undergo an end-of-treatment visit 30 days after the last dose of vemurafenib and/or cobimetinib.
Patients who discontinue the study treatment for any reason other than progression (e.g. toxicity) must be followed up every 8 weeks unless they withdraw their consent.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cobimetinib + Vemurafenib combination | Experimental | Drug: Cobimetinib + Vemurafenib combination treatmentEvery patients will be treated with : Vemurafenib 1920 mg / day from day 1 to day 28 continuously Cobimetinib 60 mg / day from day 1 to day 21 One cycle = 28 days Intervention = Cobimetinib + Vemurafenib combination treatment. Only one arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Men and women ≥ 18 years of age.
- Histologically confirmed metastatic cutaneous melanoma, mucous melanoma, or melanoma of unknown primary origin (stage IV).
- Documented BRAFV600 mutation determined in a hospital center specializing in the molecular genetics of cancer that is certified by the French national cancer institute (INCa).
- Presence of Brain Metastases (BM) for which surgical resection is not a reasonable treatment option but that may be amenable to treatment with targeted therapy, to be decided in the onco-dermatology and/or neuro-oncology multidisciplinary team meeting (MDTM).
- At least one measurable BM in at least one dimension between 5 and 40 mm on magnetic resonance imaging (MRI) with gadolinium (modified RECIST 1.1).
Key exclusion criteria (29 listed)
- Uveal melanoma. Patients with mucous melanoma or melanoma of unknown primary origin are eligible if BRAFV600 mutation is confirmed.
- Symptomatic or diffuse leptomeningeal involvement.
- Symptoms of uncontrolled intracranial pressure. Increasing corticosteroid dose during the 7 days prior to the first dose of the study treatment is an exclusion criterion. Patients receiving corticosteroids and patients presenting intermittent seizures may be enrolled if the dose of corticosteroids and anti-epileptic treatments has been stable for at least 2 weeks before inclusion.
- Indication for urgent neurosurgery or radiotherapy.
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been treated to complete remission or untreated stage I chronic lymphoid leukemia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cobimetinib + Vemurafenib combination treatmentAlso: Vemurafenib = Zelboraf (commercial name), Cobimetinib = code number RO5514041/F04Patients will be treated from day 1 to day 28 with Vemurafenib and from day 1 to day 21 with Cobimetinib. Day 1 to Day 28 corresponds to one cycle of treatment. | Drug | Cobimetinib + Vemurafenib combination |
Primary outcome
Complete or partial intracranial response rate in cohort A on the evaluation of each patient's best tumor response by the centralized review committee according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.
Time frame: From baseline up to 36 months
7 secondary outcomes
Complete or partial intracranial response rates in cohorts B and C based on the evaluation of each patient's best tumor response by the centralized review committee according to modified RECIST 1.1 criteria.
Time frame: Up to 36 months
Intracranial duration of response (DR) in cohorts A, B and C.
Time frame: Up to 36 months
Overall response rate of cohorts A, B and C
Time frame: Up to 36 months
Overall survival in cohorts A, B and C
Time frame: Up to 36 months
Frequency of Adverse events
Time frame: Up to 36 months
Overall duration of response (DR) in cohorts A, B and C.
Time frame: Up to 36 months
Patient free survival in cohorts A, B and C
Time frame: Up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thierry Lesimple, MD principal investigator
Centre Eugène Marquis
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cobimetinib + Vemurafenib combination treatment in people with Malignant Melanoma, run by Center Eugene Marquis at 17 sites in France.
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 29 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 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Complete or partial intracranial response rate in cohort A on the evaluation of each patient's best tumor response by the centralized review committee according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. (time frame: From baseline up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jan 2020.