Pembrolizumab and Chemoradiotherapy for the Treatment of Unresectable Gastroesophageal Cancer

NCT04522336 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2019-1253NCI-2020-05251
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial investigates how well pembrolizumab and chemoradiotherapy works in treating patients with gastroesophageal cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as fluorouracil, oxaliplatin and docetaxel 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 photons to kill tumor cells and shrink tumors. Giving pembrolizumab together with chemoradiotherapy may help to control gastroesophageal cancer.

Conditions

Localized Gastroesophageal Junction Adenocarcinoma; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8; Unresectable Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Clinical complete response (cCR)

  cCR, defined as at the time of post-chemoradiation staging, there is no evidence of cancer on endoscopic examination/histology/cytology and there is no evidence of cancer by imaging modality. Tumor assessment will be conducted every 9 weeks until the 54th week of the study and every 12 weeks after that. The best response will be recorded.

  Up to 2 years

Secondary Outcomes (7)

• Number of participants experiencing adverse events (AEs)

  Up to 90 days post treatment

• Number of participants discontinuing study drug due to AEs

  Up to 90 days post treatment

• Overall survival (OS)

  From start of treatment to death due to any cause, assessed up to 2 years

• Median progression free survival (PFS)

  From date of first dose with study drug to the earliest date of progression or death by any cause (in the absence of progression), assessed up to 2 years

• PFS at 6 months

  From date of first dose with study drug to the earliest date of progression or death by any cause (in the absence of progression), assessed at 6 months

Other Outcomes (5)

• Tumor PD-L1 proportion

  Up to 2 years

• Tumor gene expression

  Up to 2 years

• Tumor genetics

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, chemoradiotherapy)

EXPERIMENTAL

See Detailed Description

Drug: Docetaxel; Drug: Fluorouracil; Drug: Oxaliplatin; Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (pembrolizumab, chemoradiotherapy)

Fluorouracil DRUG

Given IV

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

Treatment (pembrolizumab, chemoradiotherapy)

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, chemoradiotherapy)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab, chemoradiotherapy)

Radiation Therapy RADIATION

Receive radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (pembrolizumab, chemoradiotherapy)

Eligibility Criteria

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

You may qualify if:

• Participants with histologically confirmed diagnosis of unresectable gastroesophageal adenocarcinoma will be enrolled in this study for systemic treatment first
• Have histologically documented locally advanced unresectable cancer or localized cancer in a patient who declines surgery
• Participant is able to provide endoscopic research biopsies and research blood
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to treatment initiation
• A male participant must agree to use a contraception during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatment(s) after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days/weeks after the last dose of study treatment

You may not qualify if:

• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for future biomedical research. However, the participant may participate in the main trial without participating in future biomedical research
• Absolute neutrophil count \>= 1500/uL (within 10 days prior to the start of study treatment)
• Platelets \>= 100 000/uL (within 10 days prior to the start of study treatment)
• Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (within 10 days prior to the start of study treatment)
• Criteria may be met with blood transfusion as these tumors are losing blood
• Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated\* creatinine clearance (CrCl) \>= 60 mL/min for participant with creatinine levels \> 1.5 x institutional ULN (within 10 days prior to the start of study treatment) (GFR can also be used in place of creatinine or CrCl)
• Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin =\<1.5 x ULN OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (within 10 days prior to the start of study treatment)
• International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of study treatment)
• Has cancer that is confined to the stomach and not involving gastroesophageal junction
• Has significant cardiovascular impairment within 6 months of the first dose of study drug (New York Heart Association \[NYHA\] class III or IV)
• Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention
• Has pre-existing peripheral neuropathy \> grade 1

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Docetaxel; Fluorouracil; dehydroftorafur; Oxaliplatin; pembrolizumab; Radiotherapy; Radiation

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Therapeutics; Physical Phenomena

Study Officials

• Jaffer A Ajani

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: August 13, 2020
• First Posted: August 21, 2020
• Study Start: September 16, 2020
• Primary Completion (Estimated): July 18, 2027
• Study Completion (Estimated): July 18, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (1)