A phase II, multicenter, open-label, randomized-controlled trial evaluating the efficacy and safety of a sequencing schedule of cobimetinib plus vemurafenib followed by immunotherapy with an anti- PD-L1 antibody atezolizumab for the treatment in patients with unresectable or metastatic BRAF V600 mutant melanoma - ImmunoCobiVem

niversity Hospital Essen0 sites176 target enrollmentMarch 8, 2018

ConditionsPatients with locally advanced, unresectable or metastatic BRAFV600 mutant melanoma.MedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10025667Term: Malignant melanoma site/stage unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10027480Term: Metastatic malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]

DrugsCotellic Zelboraf TECENTRIQ Cottelic

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Patients with locally advanced, unresectable or metastatic BRAFV600 mutant melanoma.
Sponsor: niversity Hospital Essen
Enrollment: 176
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

March 8, 2018

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

niversity Hospital Essen

Eligibility Criteria

Inclusion Criteria

•1\. Be willing and able to provide written informed consent for the trial.
•2\. Male or female patient being \=18 years of age on day of signing informed consent.
•3\. Histologically confirmed diagnosis of locally advanced, unresectable or metastatic melanoma AJCC 7th edition (unresectable stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c) without active or untreated brain metastases; all known CNS lesions must have been treated with stereotactic therapy or surgery at least 4 weeks prior to the first dose of trial treatment AND the patient must be without evidence of clinical or radiographic disease progression in the CNS for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms must have returned to baseline, the patient must have no evidence of new or enlarging brain metastases, and the patient must not have used steroids in dosing exceeding 10 mg daily of prednisone equivalent for at least 3 weeks prior to trial treatment .
•4\. No previous therapy for the advanced or metastatic stage. Prior adjuvant therapy is permitted (e.g. IFN, IL\-2\-therapy, chemo\- or radiotherapy). Prior adjuvant therapy has to be terminated (last dose) at least 28 days before enrollment. Patients who are in follow\-up period of a clinical trial in adjuvant setting and progressing may be enrolled / randomized.
•5\. Measurable disease, i.e., present with at least one measurable lesion per RECIST, version 1\.1, for the definition of a measureable lesion.
•6\. Presence of BRAF mutation (V600\) in tumor tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion prior to enrollment.
•7\. Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
•8\. Have a performance status of 0 or 1 on the ECOG Performance Scale.
•9\. Demonstrate adequate organ function as defined as following. All screening labs should be performed within 28 days of treatment initiation.
•9\.1 Hematological:

Exclusion Criteria

•1\. Presence of uveal melanoma
•2\. Use of any investigational or non\-registered product within the 30 days before registration.
•3\. Diagnosis of immunodeficiency or receiving systemic steroid therapy exceeding 10 mg/d of prednisone equivalent or any other form of immunosuppressive therapy within 7 days prior to study Day 1\.
•4\. Prior therapy with an anti\-PD\-1, anti\-PD\-L1, anti\-PD\-L2, anti\-CD137, or anti\-CTLA\-4 antibody (any other AB or drug specifically targeting T\-cell co\-stimulation or checkpoint pathways) also in an adjuvant setting.
•5\. Prior therapy with a BRAF inhibitor (including vemurafenib, dabrafenib, encorafenib and / or MEK inhibitor including trametinib, AZD6244, Binimetinib, Cobimetinib) also in an adjuvant setting.
•6\. Prior major surgery. Note: Subjects,may be enrolled if they have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
•7\. Known additional malignancy that is progressing or requires active treatment within 3 years prior to the study. Exceptions include adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy without evidence or recurrence.
•8\. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
•Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for \= 4 weeks prior to first dose of trial treatment and neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for \= 3 weeks prior to trial treatment.
•9\. History of leptomeningeal metastases