Clinical trial NCT05296005: Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction and Gastric Cancers
Official title: Total Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction (GEJ) and Gastric Cancers: A Pilot Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: 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
Clinical Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
Clinical Stage III Gastric Cancer AJCC v8
Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
Gastric Adenocarcinoma
Pathologic Stage IB Gastric Cancer AJCC v8
Pathologic Stage IC Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage II Gastric Cancer AJCC v8
Pathologic Stage II Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage IIA Gastric Cancer AJCC v8
Pathologic Stage IIA Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage IIB Gastric Cancer AJCC v8
Pathologic Stage IIB Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage III Gastric Cancer AJCC v8
Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage IIIA Gastric Cancer AJCC v8
Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage IIIB Gastric Cancer AJCC v8
Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8
Pathologic Stage IIIC Gastric Cancer AJCC v8
Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2022-03-25
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients able to complete all planned procedures and interventions successfully
timeFrame: Up to 24 months
measure: Incidence of adverse events
timeFrame: Up to within 30 days of discontinuation of protocol treatment
Secondary outcomes:
measure: Resident microbiota species associated with higher response
timeFrame: Up to 24 months
measure: Time to progression
timeFrame: From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
measure: Progression-free survival (PFS)
timeFrame: From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
measure: Overall survival (OS)
timeFrame: From date of treatment completion to the event of interest or otherwise censored at last follow-up, assessed up to 12 months
measure: Perfusion and early tumor uptake kinetics of primary tumor using 8F-FDG dPET/CT approaches
timeFrame: Up to 25 months
measure: 18F-FDG dPET/CT to evaluate and characterize residual primary tumor following neoadjuvant chemotherapy and initial chemoradiation therapy for subsequent adaptive boost radiation delivery.
timeFrame: Up to 12 months
Other outcomes:
measure: Standard uptake value SUVmax metrics
timeFrame: Up to 24 months
measure: Standard uptake value SUVpeak Tumor-to-liver metrics
timeFrame: Up to 24 months
measure: Standard uptake value metabolic tumor volume metrics
timeFrame: Up to 24 months
measure: Standard uptake value SUVmax Tumor-to-liver metrics
timeFrame: Up to 24 months
Locations:
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Dayssy A Diaz Pardo, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: