Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction and Gastric Cancers

Phase 1

Withdrawn

• Conditions: Clinical Stage I Gastric Cancer AJCC v8; Clinical Stage II Gastric Cancer AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8; Gastric Adenocarcinoma; Clinical Stage IIA Gastric Cancer AJCC v8; Clinical Stage IIB Gastric Cancer AJCC v8; Pathologic Stage II Gastric Cancer AJCC v8; Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
• Interventions: Drug: Capecitabine; Drug: Docetaxel; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Radiation: Radiation Therapy; Procedure: Surgical Procedure

• Registration Number: NCT05296005
• Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-12-13
• Study First Submitted QC: 2022-03-15
• Study First Posted: 2022-03-25
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-05
• Last Update Posted: 2025-02-07
• Study Start: 2025-12-31
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy, chemoradiation, surgery)	Radiation Therapy	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.
Treatment (chemotherapy, chemoradiation, surgery)	Surgical Procedure	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.
Treatment (chemotherapy, chemoradiation, surgery)	Capecitabine	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.
Treatment (chemotherapy, chemoradiation, surgery)	Fluorouracil	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.
Treatment (chemotherapy, chemoradiation, surgery)	Docetaxel	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.
Treatment (chemotherapy, chemoradiation, surgery)	Leucovorin	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.
Treatment (chemotherapy, chemoradiation, surgery)	Oxaliplatin	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Progression-free survival (PFS)	From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months	Kaplan-Meier analysis will be used to estimate PFS. PFS will include any failure (local, regional, or distant) or death from any cause.
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
Overall survival (OS)	From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months	Kaplan-Meier analysis will be used to estimate OS. OS will be death from any cause.
Perfusion and early tumor uptake kinetics of primary tumor using 8F-FDG dPET/CT approaches	Up to 25 months	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
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

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States