About this trial
Cohort 1 \[CLOSED\] Study treatment involves two segments: (1) Induction Immunotherapy segment with pembrolizumab monotherapy every 3 weeks until irRECIST PD and (2) Combination Therapy segment. Nab-paclitaxel may be utilized in place of paclitaxel at investigator's discretion for subjects with paclitaxel reactions.
Cohort 2 Patients are randomized to Arm A or B. Treatment in both arms includes pembrolizumab + RAM + paclitaxel.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18 years at the time of consent.
ECOG Performance Status (PS) of 0-1within 28 days prior to registration. NOTE: Within 0-3 days prior to the anticipated C1D1, ECOG PS must be 0-1.
Tumor tissue must be obtained from a biopsy performed either (a) prior to registration or (b) prior to C1D1, as described below.
Disqualifiers
Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease (relevant for ramucirumab).
Clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., clinically important forms of complete left bundle branch block, third degree heart block, second degree heart block, mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec, PR interval >250msec. NOTE: Investigators are encouraged to discuss potentially clinically important arrythmias with a cardiologist and consider implementing more frequent monitoring if appropriate (e.g., more frequent ECGs).
Symptomatic heart failure, uncontrolled hypokalemia despite repletion, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives. NOTE: Factors that increase risk of QTc prolongation or risk of arrhythmia, such as concomitant medications, may require increased monitoring during Combination Therapy (See Section 7).
The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
Trial design
Sequential
Treatments tested in this trial
Pembrolizumab Monotherapy
DrugPembrolizumab 200 mg IV
Ramucirumab
DrugRamucirumab 10 mg/kg IV
Paclitaxel
DrugPaclitaxel 90 mg/m2 IV
Treatment groups
Trial outcomes
Primary outcomes
Cohort 1: Evaluate the best overall response rate (BORR) by pooling Arm A and Arm B
BORR is defined as the number of best responses (including rates of complete response \[CR\], partial response \[PR\], disease control \[DCR\], stable disease \[SD\], progressive disease \[PD\]) divided by the total number of evaluable patients. Evaluate the BORR of combined ramucirumab (RAM) plus paclitaxel (with differing schedules of pembrolizumab \[PEM\]) following induction of PEM in patients with advanced gastric and GEJ adenocarcinoma pooling Arm A and B.
Cohort 2: Evaluate Progression free survival (PFS) of Ramucirumab (RAM) plus Paclitaxel plus Pembrolizumab (PEM)
PFS is defined as the time from the date of randomization to the first documented disease progression or death due to all causes, whichever occurs first. Evaluate PFS of combined ramucirumab (RAM) plus paclitaxel plus pembrolizumab (PEM) in patients with advanced gastric and GEJ adenocarcinoma with prior exposure to immunotherapy, within Arm A and Arm B separately.
Secondary outcomes
Assess the frequency and severity of adverse events
Toxicities will be measured in frequency and severity using CTCAE criteria 4.03
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Harry H Yoon
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
Merck Sharp & Dohme LLC
Collaborator
Mayo Clinic
Collaborator