Adjuvant immunotherapy with anti-PD-1 monoclonal antibody Pembrolizumab (MK-3475) versus placebo after complete resection of high-risk Stage III melanoma: A randomized, double-blind Phase 3 trial of the EORTC Melanoma Group.
- Conditions
- serious type of skin cancer caused especially by the light of the sun10040900
- Registration Number
- NL-OMON56050
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 108
Please see protocol summary section Diagnosis and main criteria for inclusion,
for full description
- At least 18 years of age.
- written informed consent must be given
- Complete resection of Stage III melanoma (AJCC R0) with histologically
confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC,
2010): Stage IIIA with metastasis > 1 mm; any Stage IIIB or IIIC. No past or
current in-transit metastases or satellitosis..
- Melanoma with unknown origin of the primary is eligible
- Mandatory to ship tumor sample for evaluation of PD-L1 expression.
- The maximum duration from surgery to first study drug treatment is 13 weeks.
Treatment should start only after complete wound healing from the surgery.
Note: If there is a delay of 1-7 days exceeding 13 weeks due to extreme
unforeseen circumstances, the eligibility should be discussed with the medical
monitor.
- Disease status for the post-surgery baseline assessment must be documented by
full Chest/Abdomen/Pelvis CT and/or MRI with Neck CT and/or MRI (for Head and
Neck primaries) and complete clinical examination after the informed consent
and prior to enrollment.
Note: if a patient had laboratory/imaging tests as part of local routine
guidelines (standard of care) prior to signing informed consent, the procedures
will be acceptable for screening purpose if they are within the window required
by the protocol.
- Disease-free (no loco-regional relapse or distant metastasis); no clinical
evidence for brain metastases.
- BRAF mutation status (known or not done)
- ECOG performance status of 0 or 1.
- Patient demonstrates adequate organ function as defined in the protocol
- Women of child bearing potential (WOCBP) must have a negative serum (or
urine) pregnancy test within 72 hours prior to the first dose of study
treatment.
- Patients of childbearing / reproductive potential should use adequate birth
control methods.
- Female patients who are breast feeding should discontinue nursing prior to
the first dose of study treatment and until 120 days after the last dose of
study drug .
- Patients who have been disease-free for 5 years, or patients with a history
of completly resected non-melanoma skin cancer or succesfully treated in situ
carcinoma are eligible, for example cervical cancer is situ. , Please refer to
the Diagnosis and Main Criteria for Inclusion in the Protocol for the full list
of inclusion criteria.
Please see protocol summary section Diagnosis and main criteria for inclusion,
for full description
- Mucosal or ocular melanoma.
- Prior therapy for melanoma including surgery for primary melanoma lesions.
- history of (non-infectious) pneumonitis that required steroids or current
pneumonitis. History of or current interstitial lung disease.
- history of another malignancy or a concurrent malignancy. Exceptions include
patients who have been disease-free for 5 years, or patients with a history of
completely resected non-melanoma skin cancer or succesfully treated in situ
carcinoma are eligible, for example cervical cancer in situ.
- active autoimmune disease that has required systemic treatment in past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
- active infection requiring therapy.
- diagnosis of immunodeficiency, no systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study
treatment
- known history of human immunodeficiency virus (HIV), active Hepatitis B or
Hepatitis C.
- treatment with live vaccines within 30 days prior to the first dose of study
medication are not eligible.
- prior treatment with any anti-CTLA4 monoclonal antibody or anti-PD-1, or
PD-L1 or PD-L2 agent.
- Patient is currently participating and receiving study therapy or has
participated in a study of an investigational agent and received study therapy
or used an investigation device within 4 weeks prior to the first dose of
treatment
- patient is or has an immediate family member (e.g., spouse, parent/legal
guardian, sibling or child) who is investigational site or Sponsor staff
directly involved with this trial, unless prospective IRB approval (by chair or
designee) is given allowing exception to this criterion for a specific subject.
- female patients who are Breast feeding
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>* Recurrence-free survival (RFS)<br /><br>* RFS for patients with PD-L1-positive expression<br /><br>* Progression/recurrence-free survival 2 (PRFS2)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints:<br /><br>* Distant metastases-free survival (DMFS)<br /><br>* DMFS for patients with PD-L1-positive expression<br /><br>* Overall survival (OS)<br /><br>* OS for patients with PD-L1-positive expression<br /><br>* Pharmacokinetics (PK) of pembrolizumab<br /><br>Adverse events will be scored according to the CTCAE version 4.0<br /><br>* Quality of life<br /><br>* Health economics<br /><br>* Predictive biomarkers (e.g. immune-related gene signatures, genetic<br /><br>variation, SPDL1) for treatment difference in outcome<br /><br>* To assess for development of anti-drug antibodies (ADA).</p><br>