Combination or Sequence of Vemurafenib, Cobimetinib, and Atezolizumab in High-risk, Resectable Melanoma (NEO-TIM)

  • STATUS
    Recruiting
  • End date
    Jun 4, 2027
  • participants needed
    88
  • sponsor
    Fondazione Melanoma Onlus
Updated on 4 May 2022
measurable disease
BRAF
vemurafenib
immunomodulators
cobimetinib
immunologic adjuvant
braf v600e mutation

Summary

Neoadjuvant plus adjuvant treatment with target therapy and immunotherapy given in combination or sequence may have an anti-tumour activity and may reduce the risk of relapse in patients with high-risk resectable melanoma (stage III B / C / D and oligometastatic stage IV).

Description

Melanoma represents a considerable health burden and an ongoing area of unmet need in oncology. Despite melanoma accounts for only 1% of diagnosed skin cancers, it is the cause of most skin cancer-related deaths. Until recently, limited effective treatment options were available to patients with advanced melanoma. Historically, response rates to conventional chemotherapy and immunomodulation therapy (interleukin-2 or interferon-γ) have been reported at approximately 5-19%.

Adjuvant immune checkpoint blockade (ICB) and target therapy improve outcomes of patients with high-risk resectable melanoma. It has recently been demonstrated that treatment with neoadjuvant and adjuvant targeted therapy (dabrafenib and trametinib) is associated with a high pathologic complete response (pCR) rate and improved outcomes over surgery alone. However, treatment with ICB has not been well studied in the neoadjuvant setting, despite preclinical studies suggesting that neoadjuvant administration of ICB is associated with improved survival and enhanced anti-tumour immune responses compared to the same therapy administered in the adjuvant setting.

The advantage of neoadjuvant trials is the availability of blood and tumour tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumour microenvironment.

Prospective neoadjuvant clinical trials with targeted (dabrafenib/trametinib combo) or immunotherapeutic agents (nivolumab alone or nivolumab/ipilimumab combo) and combinations are now running in a subgroup of highrisk melanoma patients with pooled overall promising preliminary results of high rates of pathologic complete responses (pCRs, 30-50%) and early data of positive correlation between pCR and relapse-free survival. Based on the available results to date, we aim to conduct a randomized, noncomparative phase II trial to define the role of neoadjuvant plus adjuvant target and immunotherapy, given in combination or sequence, in patients with high risk surgically resectable melanoma.This approach has the potential to define whether neoadjuvant treatment has antitumour activity and whether it reduces the risk of relapse after surgery.

Details
Condition Melanoma
Treatment Atezolizumab 1200 MG in 20 ML Injection, Cobimetinib 20 MG Oral Tablet, Vemurafenib 240 Mg Oral Capsule
Clinical Study IdentifierNCT04722575
SponsorFondazione Melanoma Onlus
Last Modified on4 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patients of either sex aged ≥18 years
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Patients must have histologically or cytologically confirmed Stage IIIB/C/D or oligometastatic stage IV1 resectable melanoma. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumour Conference attended by melanoma medical and surgical oncology staff. Resectable tumours are defined as having no significant vascular, neural or bony involvement. Only cases where a complete surgical resection with tumour-free margins can safely be achieved are defined as resectable
All patients must have a BRAF V600E/K mutation status known
Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team
Patients must have measurable disease, defined by RECIST 1.1
ECOG performance status 0-1
Patients must have organ and marrow function
Absence of any psychological, familiar or social condition that may affect compliance with study protocol and schedule follow-up
Female subjects of childbearing potential must have a negative pregnancy test result at baseline and must practice a reliable method of contraception for the total study duration plus 23 weeks (i.e. 30 days plus the time required for experimental drugs to undergo five half-lives) after the last dose of experimental drugs
Men who are sexually active with women of childbearing potential must practice a reliable method of contraception for the total study duration plus 31 weeks (i.e. 80 days plus the time required for experimental drugs to undergo five half-lives) after the last dose of experimental drugs

Exclusion Criteria

Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug
Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years
Any major surgery within the last 3 weeks
Pregnancy and/or breast feeding or of childbearing potential and not practicing a reliable method of birth control
Unwillingness or inability to follow the procedures required in the protocol
Uncontrolled diabetes, hypertension or other medical conditions that may interfere with assessment of toxicity
Current use of anticoagulants (warfarin, heparin, direct thrombin inhibitors) at therapeutic levels
Patients with a history of uncontrolled cardiovascular or interstitial lung disease and evidence or risk of retinal vein occlusion or central serous retinopathy
Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
Prior BRAF or MEK directed therapy; patients who have received prior interferon are eligible
History of retinopathy or any finding at ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular de generation
Presence of any of the following risk factors for RVO: a) Uncontrolled glaucoma with intraocular pressures ≥ 21mmHg; b) Serum cholesterol ≥Grade 2; c) Hypertriglyceridemia ≥ Grade 2; d) Hyperglycaemia (fasting) ≥Grade 2
Correct QT interval > 450msec to baseline, history of congenital long QT syndrome
Uncontrolled medical condition among which endocrine disorders (such as hypothyroidism, hyperthyroidism and diabetes mellitus)
Other severe medical or psychiatric conditions (like depression) or abnormalities of laboratory tests that may increase the risk associated with study participation or the assumption of Vemurafenib, Atezolizumab and Cobimetinib or that may interfere with the interpretation of study results, which in the judgment of the Investigator can make the patient not eligible for the study
Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, cerebrovascular accident or transient ischemic attack, pulmonary embolism, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
History of active primary immunodeficiency
Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP
Prior treatment with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Positive test for HBV sAg or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
Known history of testing positive for HIV or known AIDS
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note