Clinical trial NCT02212730: A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)
Official title: A Clinical Trial to Evaluate the Effect of Neoadjuvant MK-3475 (Pembrolizumab) Therapy on Intratumoral Immune Infiltrates in Renal Cell Cancer (RCC) Patients Undergoing Surgical Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Renal Cell Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-08-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.


Eligibility criteria: Inclusion Criteria:

* Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (\>= T1b), not previously treated, and be a candidate for operative tumor resection
* Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Demonstrate adequate organ function
* Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
* Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.

Exclusion Criteria:

* Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
* Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
* Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
* Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
* Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
* Has an active infection requiring systematic therapy
* Is receiving anticoagulant therapy, with the exception of low dosage aspirin
* Has severe cardiovascular disease or symptomatic ischemic heart disease
* Has hepatic decompensation
* Has uncontrolled thyroid dysfunction
* Has uncontrolled diabetes mellitus
* Has known psychiatric or substance abuse disorders
* Female is pregnant or breastfeeding
* Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
* Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
* Has a known history of human immunodeficiency virus (HIV)
* Has known active hepatitis B or C
* Has received a live vaccine within 30 days prior to screening

Primary outcomes:
measure: Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
timeFrame: Up to Week 16
measure: Number of Participants Who Discontinued Treatment Due to an Adverse Event
timeFrame: Up to 56 weeks
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
timeFrame: Baseline and Week 7
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
timeFrame: Baseline and Week 7
measure: Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
timeFrame: Baseline and Week 7
Secondary outcomes:
measure: Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
timeFrame: Baseline and Week 7
measure: Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
timeFrame: Baseline and Week 7
measure: Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
timeFrame: Baseline and Week 7
measure: Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
timeFrame: Baseline and Week 7
measure: Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
timeFrame: Baseline and Week 7
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: