Novel SEQUEnced Immunotherapy With Anti-angiogenesis and Chemotherapy in Advanced gastroesophageaL Adenocarcinoma

NCT04069273 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GI18-333
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Gastric Cancer; GastroEsophageal Cancer; Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  3 years

• 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.

  3 years

Secondary Outcomes (1)

• Assess the frequency and severity of adverse events

  3 years

Study Arms (2)

Arm A

EXPERIMENTAL

Pembrolizumab will be administered every 3 weeks in combination with ramucirumab + paclitaxel. The paclitaxel schedule differs between the 2 arms.

Drug: Pembrolizumab Monotherapy; Drug: Ramucirumab; Drug: Paclitaxel

Arm B

EXPERIMENTAL

Pembrolizumab will be administered every 3 weeks in combination with ramucirumab + paclitaxel. The paclitaxel schedule differs between the 2 arms.

Drug: Pembrolizumab Monotherapy; Drug: Ramucirumab; Drug: Paclitaxel

Interventions

Pembrolizumab Monotherapy DRUG

Pembrolizumab 200 mg IV

Also known as: Keytruda

Arm A; Arm B

Ramucirumab DRUG

Ramucirumab 10 mg/kg IV

Also known as: Cyramza

Arm A; Arm B

Paclitaxel DRUG

Paclitaxel 90 mg/m2 IV

Also known as: Taxol

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Prior to registration: if a biopsy was performed prior to registration and no interval systemic anti-cancer treatment was administered between the biopsy collection and C1D1, part of that tissue is required for correlative analysis, and must be identified during screening and shipped after registration. In this situation, tissue from a new biopsy is not required.
• Prior to C1D1: For all other subjects, a new biopsy prior to C1D1 is required (research biopsy per parallel biopsy protocol entitled: "Exploration of tumor biology in patients with metastatic esophageal and gastric cancer", \[biorepository protocol for prospective tissue collection\]) to obtain tissue.
• NOTE: If tissue cannot be obtained by either of the above approaches (e.g., clinically contraindicated), the subject is not eligible for trial participation.
• Willingness to provide tissue and blood samples for correlative research purposes and presence of a malignant lesion that is amenable to repeat biopsy while on study protocol (e.g., primary tumor that can be accessed by EGD).
• NOTE: Enrollment in parallel biopsy protocol, if open for enrollment, is required. Parallel biopsy protocol entitled: "Exploration of tumor biology in patients with metastatic esophageal and gastric cancer (biorepository protocol for prospective tissue collection)".
• PD-L1 results are required, if available. If PD-L1 testing has not been done, it should be ordered as standard of care prior to C1D1. PD-L1 testing must be performed by a CLIA certified lab using the Dako 22C3 antibody.
• Histologically or cytologically proven adenocarcinoma of the stomach or GEJ.
• Metastatic, recurrent, or locally advanced unresectable disease.
• Candidate for pembrolizumab, ramucirumab, and paclitaxel (or nab-paclitaxel)
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration. NOTE: Labs must also be obtained within 10 days prior to C1D1 treatment.
• Absolute Neutrophil Count (ANC) ≥ 1,100/mm3

You may not qualify if:

• 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).
• Any of the following cardiac criteria:
• 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.
• The patient has uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management.
• The patient has experienced any Grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy (relevant for ramucirumab).
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis (relevant for ramucirumab).
• Hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer (relevant for ramucirumab) that in the opinion of the investigator poses unacceptably high risk as standard clinical practice when combined with ramucirumab.
• The patient has a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) that in the opinion of the investigator poses unacceptably high risk as standard clinical practice when combined with ramucirumab.
• The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy that in the opinion of the investigator poses unacceptably high risk as standard clinical practice when combined with ramucirumab.
• The patient has undergone major surgery within 28 days prior to first dose of protocol therapy prior to the first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial (relevant for ramucirumab).
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Has active autoimmune disease that has required systemic treatment in the past 6 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) that in the opinion of the investigator poses unacceptably high risk as standard clinical practice when combined with pembrolizumab. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. NOTE: Inhaled steroids or steroid injections for joint disease are allowed.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.

Sponsors & Collaborators

• Harry H Yoon: lead
• Merck Sharp & Dohme LLC: collaborator
• Mayo Clinic: collaborator

Study Sites (2)

Mayo Clinic- Minnesota

Rochester, Minnesota, 55905, United States

RECRUITING

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma

Interventions

pembrolizumab; Ramucirumab; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Harry H Yoon, MD, MHS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Harry H Yoon, MD, MHS

CONTACT

507-284-2511; Yoon.Harry@mayo.edu

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: December 1, 2020
• Primary Completion (Estimated): June 11, 2026
• Study Completion (Estimated): December 10, 2026
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)