Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction and Gastric Cancers

Total Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction (GEJ) and Gastric Cancers: A Pilot Trial

This phase I trial tests the safety, side effects studies chemotherapy followed by chemotherapy at the same time as radiation therapy (chemoradiation) before surgery (neoadjuvant) in treating patients with stage gastric (stomach) or gastroesophageal junction cancer . Chemotherapy drugs, such as docetaxel, oxaliplatin , leucovorin, fluorouracil, and capecitabine, 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 chemotherapy and chemoradiation before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Clinical Stage III Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage I Gastric Cancer AJCC v8; Clinical Stage II Gastric Cancer AJCC v8; Clinical Stage IIA Gastric Cancer AJCC v8; Clinical Stage IIB Gastric Cancer AJCC v8; Pathologic Stage IB Gastric Cancer AJCC v8; Pathologic Stage II Gastric Cancer AJCC v8; Pathologic Stage IIA Gastric Cancer AJCC v8; Pathologic Stage IIB Gastric Cancer AJCC v8; Pathologic Stage III Gastric Cancer AJCC v8; Pathologic Stage IIIA Gastric Cancer AJCC v8; Pathologic Stage IIIB Gastric Cancer AJCC v8; Pathologic Stage IIIC Gastric Cancer AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; 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 IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8; Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
• Intervention / Treatment: Drug: Docetaxel; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Radiation Therapy; Procedure: Surgical Procedure

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of delivering tailored targeted neoadjuvant therapy with chemotherapy followed by chemoradiation and surgery in patients with gastroesophageal junction gastroesophageal junction (GEJ) and gastric cancer.

II. To assess the toxicity of delivering tailored targeted neoadjuvant therapy with chemotherapy followed by chemoradiation and surgery in patients with GEJ and gastric cancer.

SECONDARY OBJECTIVES:

I. To identify the resident microbiota species associated with higher response to the combination therapy and quantify abundance and diversity of favorable bacterial communities over the course of the therapy.

II. To evaluate local control, progression-free survival, and overall survival at 3, 6, 9, 12 and 24 months after treatment with neoadjuvant chemotherapy and chemoradiation.

III. To describe the perfusion and early tumor uptake kinetics of primary tumor targets at baseline, during and following systemic chemotherapy and chemoradiation therapies using 18F-fluorodeoxyglucose (18F-FDG) digital photon counting positron emission tomography/computed tomography (dPET/CT) approaches.

IV. To evaluate 18F-FDG dPET/CT to evaluate and characterize residual primary tumor following neoadjuvant chemotherapy and initial chemoradiation therapy for subsequent adaptive boost radiation delivery.

EXPLORATORY OBJECTIVE :

I. To explore FDG dPET standardized uptake value (SUV) metrics (e.g., SUVmax, SUVpeak, SUVmax Tumor-to-Liver, SUVpeak Tumor-to-Liver, metabolic tumor volume, etc.) on early dynamic PET perfusion, early tumor FDG uptake and delayed tumor FDG uptake to better predict pathologic response of primary tumor following multimodality therapy and surgical resection.

OUTLINE:

NEOADJUVANT CHEMOTHERAPY: Patients receive FLOT chemotherapy consisting of docetaxel intravenously (IV) , oxaliplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on day 1 or FOLFOX chemotherapy consisting of oxaliplatin IV and leucovorin IV, and fluorouracil IV continuously over 24 hours on days 1 and 2. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.

NEOADJUVANT CHEMORADIATION: Within 4 weeks after completing neoadjuvant chemotherapy, patients undergo radiation therapy in 25 fractions over 5 weeks. Patients also receive either fluorouracil IV continuously for 24 hours on days 1-5 or capecitabine orally (PO) twice daily (BID) on days 1-5. Cycles repeat weekly for 5 weeks in the absence of disease progression or unacceptable toxicity.

SURGERY: Within 4-8 weeks after neoadjuvant chemoradiation, patients undergo surgical resection according to tumor location and per surgeon expertise.

After completion of study treatment, patients are followed up for 24 months.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
      • Contact: Dayssy A. Diaz Pardo, MD, MS; Phone Number: 614-293-3250; Email: dayssy.diazpardo@osumc.edu
      • Principal Investigator: Dayssy A. Diaz Pardo, MD, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histologically proven, cT2N0-T4aN3M0 (TNM 8th edition), gastric or Siewert II-III GEJ adenocarcinoma
• Evaluation with endoscopic ultrasound (EUS) and staging laparoscopy prior to enrollment is strongly recommended.
• Patient should be a candidate for neoadjuvant chemotherapy with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) or fluorouracil and oxaliplatin (FOLFOX).
• Patients should be >= 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patient should be eligible for surgical intervention
• T1 N0 disease (assessed by endoscopic ultrasound)

Exclusion Criteria:

• Evidence of distant metastatic disease
• Solitary functioning kidney within the potential radiation field
• Peripheral polyneuropathy > National Cancer Institute (NCI) grade II

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (chemotherapy, chemoradiation, surgery); NEOADJUVANT CHEMOTHERAPY: Patients receive FLOT chemotherapy consisting of docetaxel intravenously (IV) , oxaliplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on day 1 or FOLFOX chemotherapy consisting of oxaliplatin IV and leucovorin IV, and fluorouracil IV continuously over 24 hours on days 1 and 2. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. NEOADJUVANT CHEMORADIATION: Within 4 weeks after completing neoadjuvant chemotherapy, patients undergo radiation therapy in 25 fractions over 5 weeks. Patients also receive either fluorouracil IV continuously for 24 hours on days 1-5 or capecitabine orally (PO) twice daily (BID) on days 1-5. Cycles repeat weekly for 5 weeks in the absence of disease progression or unacceptable toxicity. SURGERY: Within 4-8 weeks after neoadjuvant chemoradiation, patients undergo surgical resection according to tumor location and per surgeon expertise.

Drug: Docetaxel; Given IV; Other Names: Taxotere; Docecad; RP56976; Taxotere Injection Concentrate; Drug: Fluorouracil; Given IV; Other Names: 5-Fluracil; Fluracil; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Drug: Leucovorin; Given IV; Other Names: Folinic acid; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; Ai Heng; Aiheng; Diaminocyclohexane Oxalatoplatinum; Eloxatine; JM-83; Oxalatoplatin; Oxalatoplatinum; RP 54780; RP-54780; SR-96669; Drug: Capecitabine; Given PO; Other Names: Xeloda; Ro 09-1978/000; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Procedure: Surgical Procedure; Undergo surgical resection; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients able to complete all planned procedures and interventions successfully	Up to 24 months
Incidence of adverse events	Up to within 30 days of discontinuation of protocol treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resident microbiota species associated with higher response		Up to 24 months
Time to progression		From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
Progression-free survival (PFS)	Kaplan-Meier analysis will be used to estimate PFS. PFS will include any failure (local, regional, or distant) or death from any cause.	From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
Overall survival (OS)	Kaplan-Meier analysis will be used to estimate OS. OS will be death from any cause.	From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
Perfusion and early tumor uptake kinetics of primary tumor using 8F-FDG dPET/CT approaches	To describe the perfusion and early tumor uptake kinetics of primary tumor targets at baseline, during and following systemic chemotherapy and chemoradiation therapies using 18F-FDG dPET/CT approaches	Up to 25 months
18F-FDG dPET/CT to evaluate and characterize residual primary tumor following neoadjuvant chemotherapy and initial chemoradiation therapy for subsequent adaptive boost radiation delivery.		Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard uptake value SUVmax metrics	Will explore 18F-fluorodeoxyglucose (FDG) digital photon counting positron emission tomography (dPET) SUV metrics (e.g., SUVmax, SUVpeak, SUVmax Tumor-to-Liver, SUVpeak Tumor-to-Liver, metabolic tumor volume, etc.) on early dynamic PET perfusion, early tumor FDG uptake and delayed tumor FDG uptake to better predict pathologic response of primary tumor following multimodality therapy and surgical resection.	Up to 24 months
Standard uptake value SUVpeak Tumor-to-liver metrics	Will explore 18F-fluorodeoxyglucose (FDG) digital photon counting positron emission tomography (dPET) SUV metrics (e.g., SUVmax, SUVpeak, SUVmax Tumor-to-Liver, SUVpeak Tumor-to-Liver, metabolic tumor volume, etc.) on early dynamic PET perfusion, early tumor FDG uptake and delayed tumor FDG uptake to better predict pathologic response of primary tumor following multimodality therapy and surgical resection.	Up to 24 months
Standard uptake value metabolic tumor volume metrics	Will explore 18F-fluorodeoxyglucose (FDG) digital photon counting positron emission tomography (dPET) SUV metrics (e.g., SUVmax, SUVpeak, SUVmax Tumor-to-Liver, SUVpeak Tumor-to-Liver, metabolic tumor volume, etc.) on early dynamic PET perfusion, early tumor FDG uptake and delayed tumor FDG uptake to better predict pathologic response of primary tumor following multimodality therapy and surgical resection.	Up to 24 months
Standard uptake value SUVmax Tumor-to-liver metrics	Will explore 18F-fluorodeoxyglucose (FDG) digital photon counting positron emission tomography (dPET) SUV metrics (e.g., SUVmax, SUVpeak, SUVmax Tumor-to-Liver, SUVpeak Tumor-to-Liver, metabolic tumor volume, etc.) on early dynamic PET perfusion, early tumor FDG uptake and delayed tumor FDG uptake to better predict pathologic response of primary tumor following multimodality therapy and surgical resection.	Up to 24 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Investigators: Principal Investigator: Dayssy A Diaz Pardo, MD, MS, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Anticipated): May 31, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Neoplasms; Adenocarcinoma; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Docetaxel; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin
• Other Study ID Numbers: OSU-20191; NCI-2021-11289 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No