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Radiation Therapy

Jaffer A Ajani

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.

PRIMARY OBJECTIVE:

I. To evaluate the clinical activity (as assessed by complete clinical response rate) of pembrolizumab plus chemoradiation.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of pembrolizumab plus chemoradiation.

II. To determine the overall survival efficacy of pembrolizumab plus chemoradiation.

III. Evaluate progression free survival (PFS) by local investigator review and by blinded central radiologists' review.

EXPLORATORY OBJECTIVES:

I. To explore the association between PD-L1 expression by immunohistochemistry, somatic gene expression profiling, and clinical efficacy of pembrolizumab.

II. To explore the relationship between genomic variation and response to study treatment.

III. To identify molecular (genomic, metabolic, and/or proteomic) biomarkers that may correlate with clinical response/resistance, safety, pharmacodynamic activity, and/or the mechanism of action of pembrolizumab in combination with chemoradiation.

IV. To determine the effect of pembrolizumab plus chemoradiation treatment on tumor T cell infiltration.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment with pembrolizumab repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive oxaliplatin IV over 2 hours on day 1 followed by fluorouracil IV over 48 hours once every 2 weeks (Q2W) for 8 weeks (4 cycles) in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION CHEMORADIATION: After a 3 week treatment free period, patients receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 3 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive fluorouracil IV continuous over 5 days (Monday through Friday) for 5 weeks and docetaxel IV over 1 hour once a week (QW) for 5 weeks in the absence of disease progression or unacceptable toxicity. Starting no later than 3 days after the beginning of the Consolidation Chemoradiation period, patients also undergo 28 fractions of radiation therapy in the absence of disease progression or unacceptable toxicity.

After a 6-9 week treatment free period, patients continue pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 3 weeks for up to 30 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 9-12 weeks thereafter.

Pembrolizumab and Chemoradiotherapy for the Treatment of Unresectable Gastroesophageal Cancer

A Pilot Trial of Pembrolizumab Plus Chemoradiotherapy in Participants With Unresectable Gastroesophageal Cancer

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.

Safety and tolerability will be assessed by clinical review of all relevant parameters including AEs, laboratory tests, and vital signs. Counts and percentages of subjects with AEs will be provided.

OS will be estimated using Kaplan-Meier method.

PFS will be estimated using Kaplan-Meier method.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pembrolizumab and Chemoradiotherapy for the Treatment of Unresectable Gastroesophageal Cancer	NCT04522336	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Localized Gastr... Locally Advance... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Unresectable Ga...	Docetaxel Fluorouracil Oxaliplatin Pembrolizumab Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Pembrolizumab and Chemoradiotherapy for the Treatment of Unresectable Gastroesophageal Cancer	NCT04522336	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Localized Gastr... Locally Advance... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Unresectable Ga...	Docetaxel Fluorouracil Oxaliplatin Pembrolizumab Radiation Thera...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for localized gastroesophageal junction adenocarcinoma