Pembrolizumab, Combination Chemotherapy, and Radiation Therapy Before Surgery in Treating Adult Patients With Locally Advanced Gastroesophageal Junction or Gastric Cardia Cancer That Can Be Removed by Surgery

NCT02730546 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: MC1541NCI-2016-0050815-005311
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

This phase Ib/II trial studies the side effects and best way to give pembrolizumab with combination chemotherapy and radiation therapy before surgery and to see how well it works in treating adult patients with gastroesophageal junction or gastric cardia cancer that has spread from where it started to nearby tissue and can be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab, combination chemotherapy, and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Gastric Cardia Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Stage IB Gastric Cancer AJCC v7; Stage II Gastric Cancer AJCC v7; Stage IIA Gastric Cancer AJCC v7; Stage IIB Gastric Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (PathCR) Rate

  Defined as number of patients with pathologic complete responses (pCR) divided by total evaluable patients. pCR is defined as no recognized cancer and margins free of tumor as found by the pathologist following resection of the esophageal specimen and accompanying lymph nodes.

  Up to 3 years

Secondary Outcomes (6)

• Complete Resection With no Tumor Within 1 mm of the Resection Margins (R0) Rate

  Up to 3 years

• Disease-free Survival (DFS)

  Up to 3 years

• Time to Relapse (TTR)

  Up to 3 years

• Overall Survival (OS) at Two Years

  2 years

• Progression-free Survival (PFS) Rate at Two Years

  2 years

Study Arms (1)

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

EXPERIMENTAL

See Detailed Description

Drug: Carboplatin; Procedure: Computed Tomography; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Drug: Paclitaxel; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Interventions

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, RADIATION, Radiotherapeutics, radiotherapy, RT, Therapy, Radiation

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo curative-intent surgery

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computerized Axial Tomography, computerized tomography, CT, CT SCAN, tomography

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, chemotherapy, radiation, surgery)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma involving the gastroesophageal junction or gastric cardia
• Central pathology review to determine evaluability of archived esophagogastroduodenoscopy (EGD)/biopsy sample
• NOTE: If archived sample was collected \> 8 weeks prior to pre-registration (reg), is not available in a timely manner, or was collected outside of Mayo Clinic and considered unevaluable, then baseline EGD with primary tumor biopsy at Mayo Clinic must be performed unless clinically contraindicated; patient is allowed to enroll regardless of whether this Mayo Clinic tissue sample is evaluable; (Only 1 EGD with primary tumor biopsy performed at Mayo Clinic =\< 8 weeks prior to pre-reg is required)
• NOTE: For both archival or newly obtained tissue, only biopsies are adequate (fine needle aspiration \[FNA\] is not adequate)
• Willing to provide mandatory tissue samples for research purposes
• Baseline imaging with an fludeoxyglucose (FDG)-positron emission tomography (PET) scan negative for distant metastatic disease must be obtained =\< 28 days prior to registration
• Surgically resectable (T2N0, T3N0, Tany with node positivity, M0), as determined by endoscopic ultrasound (EUS) and the following minimum diagnostic work-up:
• Whole-body PET/computed tomography (CT) (PET/CT of skull base to mid-thigh is acceptable)
• EUS =\< 21 days prior to registration
• NOTE: Patients may have regional adenopathy including para-esophageal, gastric, gastrohepatic and celiac nodes; if celiac adenopathy is present, it must be \< 2 cm
• NOTE: If patient unable to have PET/CT then CT chest/abdomen/pelvis with contrast (preferred) or MRI chest/abdomen/pelvis with contrast
• Surgical consultation at enrolling site to confirm that patient will be able to undergo curative resection after completion of chemoradiation =\< 56 days prior to registration
• Tumor is amenable to standard resection and reconstruction
• Radiation oncology consultation at enrolling site to confirm that disease can be encompassed in a radiotherapy field =\< 56 days prior to registration
• NOTE: Radiotherapy quality assurance rapid review must be performed before the first fraction of radiation therapy (RT) is administered; if RT constraints cannot be met, the patient will be removed from the protocol prior to treatment

You may not qualify if:

• Tumor characteristics - any of the following are excluded:
• Evidence of distant metastases
• Tumors whose location is restricted to the tubular esophagus (i.e., without involvement of the GEJ or cardia)
• Tumors whose proximal end are at the level of the carina or higher
• Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula
• Palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (\> 1.5 cm in greatest dimension)
• T1N0M0, T4Nany, or in situ carcinoma
• Tumor must not extend 5 or more cm into the stomach
• Received prior treatment or receiving current treatment for this malignancy
• Prior radiation to chest or abdomen, or to \> 30% of the marrow cavity
• Inadequate caloric or fluid intake whereby there is a current or likely future need for enteral or parenteral feeding during chemoradiation or the preoperative period
• Major surgery =\< 4 weeks prior to registration
• Active autoimmune disorders, including patients known to be human immunodeficiency virus (HIV) positive, or those requiring chronic steroid administration (excluding inhaled steroids)
• Uncontrolled diabetes (i.e., will interfere with the performance of the FDG PET/CT scans)
• Prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine, or study drugs involved in this protocol, or to a monoclonal antibody or prior hypersensitivity to platinum-containing agents

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Carboplatin; Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin; Paclitaxel; Taxes; pembrolizumab; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Harry H Yoon MD MHS
• Organization: Mayo Clinic

yoon.harry@mayo.edu

507-284-2511

Study Officials

• Harry H. Yoon, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2016
• First Posted: April 6, 2016
• Study Start: June 24, 2016
• Primary Completion: July 1, 2021
• Study Completion: October 31, 2023
• Last Updated: June 22, 2025
• Results First Posted: August 25, 2022

Record last verified: 2024-04

Locations

US (2)