Perioperative Chemo and Pembrolizumab in Gastric Cancer

NCT02918162 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAQ9871
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 4

Brief Summary

This is a non-randomized, multi-site, open-label trial of pembrolizumab and chemotherapy in subjects with gastric or gastroesophageal (GE) junction adenocarcinoma. The purpose of this study is to determine and evaluate the efficacy of combination therapy with immune checkpoint blockade and chemotherapy used in the perioperative period in eradicating micrometastatic disease; and to compare paired tissue and serum samples (pre-treatment and post-treatment) from individually treated patients to explore the immune effects of combination therapy and predictors of response.

Conditions

Gastric Cancer; Adenocarcinoma of the Gastroesophageal Junction

Keywords

pembrolizumab; adenocarcinoma; gastric cancer; Locoregional gastric adenocarcinoma; Locoregional GE junction adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response (pCR) Rate

  Number of subjects with absence of viable tumor on surgical resection specimen as determined by local pathology review.

  Up to 34 months

Secondary Outcomes (3)

• Overall Survival (OS)

  Treatment initiation until death or study end, whichever occurs first (up to approximately 5 years)

• Disease Free Survival (DFS)

  Treatment initiation to progression, recurrence, death or study end, whichever comes first (up to approximately 5 years)

• Overall Response Rate (ORR)

  Up to 34 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

All study subjects will receive standard of care chemotherapy regimen for 3 cycles prior to and 3 cycles following surgery in combination with Pembrolizumab with an additional cycle of Pembrolizumab (4 total) in the pre-operative period. Additionally subjects will complete 12 months of maintenance Pembrolizumab (14 additional doses to complete 17 post-operative cycles) following completion of post-operative chemotherapy. Standard of care combination chemotherapy regimen has a 21-day cycle.

Drug: Pembrolizumab; Drug: Standard of care chemotherapy regimen

Interventions

Pembrolizumab DRUG

Pembrolizumab dosed IV at 200mg every 21 days per cycle.

Also known as: KEYTRUDA, MK-3475

Pembrolizumab

Standard of care chemotherapy regimen DRUG

Standard regimen containing at least a platinum and Fluorouracil (5-FU) agent (per National Comprehensive Cancer Network guidelines) - such as Doublet or Triplet chemotherapy with capecitabine, oxaliplatin, and epirubicin (optional) (21 day cycle). Epirubicin can be excluded at the discretion of the treating physician. Example: Oxaliplatin dosed IV at 130 mg/m2 every 21 days per cycle. Capecitabine dosed orally at 625mg/m2 twice a day daily.

Also known as: Investigator's choice of of standard regimen

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Have previously untreated localized gastric or GE junction adenocarcinoma as defined by T2 or greater primary lesion or the presence of any positive nodes- N+(clinical nodes) without evidence of metastatic disease.
• Plan to proceed to surgery following peri-operative chemotherapy based on standard staging studies per local practice.
• Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
• Be at least 18 years of age on day of signing informed consent.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation.
• Adequate Organ Function Laboratory Values
• Absolute neutrophil count (ANC) ≥1,500 /mcL
• Platelets ≥100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin \>2.5 mg/dL

You may not qualify if:

• 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.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids (prednisone 10 mf or equivalent) may be approved after consultation.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for their current diagnosis.
• Has a known additional malignancy that is progressing or requires active treatment within 3 years from registration. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. Subjects with a history of prior malignancy diagnosed and treated greater than 3 years form registration may be considered with consultation of the primary investigator.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the 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.
• Has known history of prior pneumonitis requiring treatment with steroids, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy which is not expected to have resolved by Cycle 1 Day 1 dosing.
• Has a history or current evidence of any condition (e.g. known deficiency of the enzyme dihydropyrimidine dehydrogenase \[DPD\]),, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• Gulam Manji: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Haesong Park

St Louis, Missouri, 63130, United States

Location

Weill Cornell Medical College/ NewYork-Presbyterian

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Brown University

Providence, Rhode Island, 02912, United States

Location

Related Publications (1)

• Manji GA, Lee S, Del Portillo A, May M, Ana SS, Alouani E, Sender N, Negri T, Gautier K, Ge L, Fan W, Xie M, Sethi A, Schrope B, Tan AC, Park H, Oberstein PE, Shah MA, Raufi AG. Chemotherapy and Immune Checkpoint Blockade for Gastric and Gastroesophageal Junction Adenocarcinoma. JAMA Oncol. 2023 Dec 1;9(12):1702-1707. doi: 10.1001/jamaoncol.2023.4423.

  PMID: 37856106 DERIVED

Related Links

• Cancer Center's clinical trials online search tool

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma

Interventions

pembrolizumab

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

Results Point of Contact

• Title: Gulam Manji, MD, PhD
• Organization: Columbia University

gam2140@cumc.columbia.edu

212-305-7115

Study Officials

• Gulam Manji, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 27, 2016
• First Posted: September 28, 2016
• Study Start: November 25, 2017
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: February 15, 2024
• Results First Posted: February 15, 2024

Record last verified: 2024-01

Locations

US (4)