Stage IIIB-C MelanomaPhase 2NCT03005639
ML29255 Neoadjuvant Vemurafenib and Cobimetinib Melanoma
A Phase 2 study testing Vemurafenib and Cobimetinib in people with Stage IIIB-C Melanoma, run by Inova Health Care Services at 1 site in United States.
Trial summary
Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma To evaluate the overall radiological complete response rate in patients with stage IIIB/C melanoma after 8 weeks of neoadjuvant vemurafenib and cobimetinib Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIB-C Melanoma
- What is being tested?
- Vemurafenib and Cobimetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 24 Feb 2018
- 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
None listed.
Who cannot join
- Had prior radiotherapy at lymph node basin
- Prior treatment with BRAF inhibitor or MEK inhibitor
- Active infection
- Pregnant, lactating or breast feeding women
- Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- History of malabsorption or other condition that would interfere with absorption of vemurafenib or cobimetinib
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- Any underlying medical or psychiatric condition, which in the opinion of the Investigator will make the administration of vemurafenib and cobimetinib hazardous
- Unwillingness or inability to comply with study and follow-up procedures.
- The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment:
- St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
- Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)
Trial locations and contacts
1 site in 1 country.
United States1 site
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
About this study
Official title: Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
- To evaluate the overall radiological complete response rate in patients with stage IIIB/C melanoma after 8 weeks of neoadjuvant vemurafenib and cobimetinib
Read the detailed description
Vemurafenib and cobimetinib are FDA-approved drugs to treat advanced melanoma that has a mutated (changed) form of a cell protein called BRAF (BRAF V600 mutation). The purpose of this study is to determine if vemurafenib and cobimetinib can be safely given to patients with this type of melanoma to shrink it before surgery. This research is being done because patients with melanoma spread to lymph node have high chance of melanoma recurrence even after lymph node removal surgery, and currently there is no approved medicine to use for patients with BRAF V600 mutant melanoma before lymph node removal surgery.
Vemurafenib and cobimetinib as a combination has been approved by the United States Food and Drug Administration (FDA) for patients with more advanced melanoma. In this trial, vemurafenib and cobimetinib combination is considered to be experimental since safety of this combination prior to lymph node surgery has not been studied.
Before the participant begins the study:
The participant will need to have the following exams, tests or procedures to find out if eligibility is met.
- A skin exam
- An eye exam
- An electrocardiogram (ECG) which is a test that tracks the electricity of the heart
- An echocardiogram (a test that uses sound waves to create pictures of the heart) or MUGA scan (a test that uses radioactive materials called tracers to show the heart chambers) which is a test to evaluate the function of the heart
- A blood test
- A biopsy of lymph node
If the exams and tests listed above show that the individual can take part in the study, and he or she chooses to take part, then the participant will take the study drugs for 8weeks. He/she will take vemurafenib 240mg 4tablets twice daily for 56days and cobimetinib 20mg 3 tablets daily on days 1-21 and 29-49. While taking these pills, the following extra exams and tests will be needed.
- Four extra blood samples will be drawn. One blood sample will be drawn immediately before the first dose of the vemurafenib and trametinib pills. Then blood sample will be drawn 2 weeks, 4weeks, and 8weeks after starting the pills.
- A biopsy of lymph node will be performed 2weeks after starting the pills.
- Skin exams will be performed immediately before the first dose, 2weeks, 4weeks, and 8weeks after starting the pills.
- Eye exams will be performed 4weeks, 8weeks after starting the pills.
- An ECG will be performed 2weeks, 4weeks, and 8weeks after starting the pills.
- An echocardiogram or MUGA scan will be performed 4weeks after starting the pills.
- A CT scan will be performed 8weeks after starting the pills.
Once the participant finishes 8weeks of study drugs, he or she will undergo surgery within a week. After surgery, the individual will need the following extra exam.
- A skin exam A blood sample will be taken for the study at the first study visit, two week visit and eight week visit. Tissue from a core biopsy will be taken for the study at the first study visit and two week visit. This sample is required in order for the individual to take part in this study because the research on the sample is an important part of the study. The research biopsy is done in a similar way to biopsies done for diagnosis. Neither the participant nor the participant's health care plan/insurance carrier will be billed for the collection of the blood and tissue sample that will be used for this study. The results will not be made available to the participant during participation in the trial.
- Conditions
- Stage IIIB-C Melanoma
- Being tested
- Vemurafenib and Cobimetinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vemurafenib and CobimetinibDrug
Also called Zelboraf for vemurafenib
All participants will receive study treatment for up to 56 days (8 weeks). After completing treatment, they will undergo a lymph node removal surgery. After surgery, they will have follow-up visit 2-4 weeks after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Vemurafenib/Cobimetinib | Experimental | Vemurafenib and cobimetinib as a combination has been approved by the United States Food and Drug Administration (FDA) for patients with more advanced melanoma. In this trial, vemurafenib and cobimetinib combination is considered to be experimental since safety of this combination prior to lymph node surgery has not been studied. Receives: Drug: Vemurafenib and Cobimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiologic Complete Response Rate
Radiologic complete response rate will be the primary endpoint. This will be assessed after completion of the 8-week treatment of vemurafenib and cobimetinib by CT measurements of tumor diameter pre-treatment and at day 56 (± 3 days) using RECIST 1.1. Complete response (CR) is defined by a reduction in the short-axis diameter of any pathologic lymph node to less than 10 mm, whereas partial response (PR) is defined as 30% or more decrease in the short axis. The analysis of response rate is based on the efficacy evaluable patients who has post-treatment CT scan at Day 43. Patients who discontinued study drug or withdraw from the study will be included only if they had post-treatment CT scan. We will calculate radiologic complete response rate with 95% confidence interval.
Measured: Day 56 (+/- 3 days)
Secondary outcomes (1)
Overall response rate, pathologic complete response rate
Overall response rate is defined as the proportion of the patients in the analysis population who have a CR or PR. Pathologic complete response is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of all sampled lymph nodes +/- primary melanoma specimen following completion of neoadjuvant systemic therapy (ypT0ypN0 in the current AJCC staging system). The analysis of pathologic response is based on the efficacy evaluable patients who underwent therapeutic lymph node dissection. Patients who discontinued study drug or withdraw from the study will be included only if they underwent therapeutic lymph node dissection. We will calculate the pathological complete response rate with 95% confidence interval.
Measured: Day 56 (+/- 3 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study start1 Jun 2017
- Primary completion24 Feb 2018
- Study completion24 Feb 2018
Why it stopped: Sponsor has decided to close study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IIIB-C 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inova Health Care Services
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Sekwon Jang, MD, Principal investigator, Inova Schar Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03005639
- Sponsor's protocol ID
- 16-2316
- Status last verified
- May 2018
- First submitted
- 2 May 2016
- Last updated
- 9 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
- ClinicalTrials.gov ID
- NCT03005639
- Acronym / sponsor ID
- 16-2316
- Conditions
- Stage IIIB-C Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor has decided to close study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Inova Health Care ServicesUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 24 Feb 2018 (actual)
- Study completion
- 24 Feb 2018 (actual)
- First posted
- 29 Dec 2016 (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.
Neoadjuvant Vemurafenib and Cobimetinib in BRAF V600 Mutant Stage IIIB-C Melanoma
- To evaluate the overall radiological complete response rate in patients with stage IIIB/C melanoma after 8 weeks of neoadjuvant vemurafenib and cobimetinib
Detailed description
Vemurafenib and cobimetinib are FDA-approved drugs to treat advanced melanoma that has a mutated (changed) form of a cell protein called BRAF (BRAF V600 mutation). The purpose of this study is to determine if vemurafenib and cobimetinib can be safely given to patients with this type of melanoma to shrink it before surgery. This research is being done because patients with melanoma spread to lymph node have high chance of melanoma recurrence even after lymph node removal surgery, and currently there is no approved medicine to use for patients with BRAF V600 mutant melanoma before lymph node removal surgery.
Vemurafenib and cobimetinib as a combination has been approved by the United States Food and Drug Administration (FDA) for patients with more advanced melanoma. In this trial, vemurafenib and cobimetinib combination is considered to be experimental since safety of this combination prior to lymph node surgery has not been studied.
Before the participant begins the study:
The participant will need to have the following exams, tests or procedures to find out if eligibility is met.
- A skin exam
- An eye exam
- An electrocardiogram (ECG) which is a test that tracks the electricity of the heart
- An echocardiogram (a test that uses sound waves to create pictures of the heart) or MUGA scan (a test that uses radioactive materials called tracers to show the heart chambers) which is a test to evaluate the function of the heart
- A blood test
- A biopsy of lymph node
If the exams and tests listed above show that the individual can take part in the study, and he or she chooses to take part, then the participant will take the study drugs for 8weeks. He/she will take vemurafenib 240mg 4tablets twice daily for 56days and cobimetinib 20mg 3 tablets daily on days 1-21 and 29-49. While taking these pills, the following extra exams and tests will be needed.
- Four extra blood samples will be drawn. One blood sample will be drawn immediately before the first dose of the vemurafenib and trametinib pills. Then blood sample will be drawn 2 weeks, 4weeks, and 8weeks after starting the pills.
- A biopsy of lymph node will be performed 2weeks after starting the pills.
- Skin exams will be performed immediately before the first dose, 2weeks, 4weeks, and 8weeks after starting the pills.
- Eye exams will be performed 4weeks, 8weeks after starting the pills.
- An ECG will be performed 2weeks, 4weeks, and 8weeks after starting the pills.
- An echocardiogram or MUGA scan will be performed 4weeks after starting the pills.
- A CT scan will be performed 8weeks after starting the pills.
Once the participant finishes 8weeks of study drugs, he or she will undergo surgery within a week. After surgery, the individual will need the following extra exam.
- A skin exam A blood sample will be taken for the study at the first study visit, two week visit and eight week visit. Tissue from a core biopsy will be taken for the study at the first study visit and two week visit. This sample is required in order for the individual to take part in this study because the research on the sample is an important part of the study. The research biopsy is done in a similar way to biopsies done for diagnosis. Neither the participant nor the participant's health care plan/insurance carrier will be billed for the collection of the blood and tissue sample that will be used for this study. The results will not be made available to the participant during participation in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vemurafenib/Cobimetinib | Experimental | Drug: Vemurafenib and CobimetinibVemurafenib and cobimetinib as a combination has been approved by the United States Food and Drug Administration (FDA) for patients with more advanced melanoma. In this trial, vemurafenib and cobimetinib combination is considered to be experimental since safety of this combination prior to lymph node surgery has not been studied. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- Had prior radiotherapy at lymph node basin
- Prior treatment with BRAF inhibitor or MEK inhibitor
- Active infection
- Pregnant, lactating or breast feeding women
- Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
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 |
|---|---|---|
| Vemurafenib and CobimetinibAlso: Zelboraf for vemurafenibAll participants will receive study treatment for up to 56 days (8 weeks). After completing treatment, they will undergo a lymph node removal surgery. After surgery, they will have follow-up visit 2-4 weeks after surgery. | Drug | Vemurafenib/Cobimetinib |
Primary outcome
Radiologic Complete Response Rate
Time frame: Day 56 (+/- 3 days)
Radiologic complete response rate will be the primary endpoint. This will be assessed after completion of the 8-week treatment of vemurafenib and cobimetinib by CT measurements of tumor diameter pre-treatment and at day 56 (± 3 days) using RECIST 1.1. Complete response (CR) is defined by a reduction in the short-axis diameter of any pathologic lymph node to less than 10 mm, whereas partial response (PR) is defined as 30% or more decrease in the short axis. The analysis of response rate is based on the efficacy evaluable patients who has post-treatment CT scan at Day 43. Patients who discontinued study drug or withdraw from the study will be included only if they had post-treatment CT scan. We will calculate radiologic complete response rate with 95% confidence interval.
1 secondary outcome
Overall response rate, pathologic complete response rate
Time frame: Day 56 (+/- 3 days)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2018.
- 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.
Sekwon Jang, MD principal investigator
Inova Schar Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vemurafenib and Cobimetinib in people with Stage IIIB-C Melanoma, run by Inova Health Care Services at 1 site in United States.
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 0 inclusion and 11 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: withdrawn, as of the sponsor's last update on 9 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Radiologic Complete Response Rate (time frame: Day 56 (+/- 3 days)). 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 9 May 2018.