Folfox+Irinotecan+Chemort In Esophageal Cancer

A Phase II Study of Neoadjuvant NAPOX Followed by Chemoradiation With Paclitaxel and Carboplatin in Locally Advanced Esophagogastric Cancer

In this research study, is studying how Liposomal Irinotecan in combination with the standard of care interventions FOLFOX, carboplatin paclitaxel, and radiation therapy affect gastroesophageal junction or esophagogastric cancer

This research study involves the following study intervention:

- Liposomal irinotecan

Study Overview

• Status: Recruiting
• Conditions: Esophagogastric Cancer; Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: FOLFOX/ nal-IRI; Drug: Paclitaxel; Drug: Carboplatin; Radiation: Proton Radiation Therapy

Detailed Description

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

This research study involves the following standard of care interventions:

• FOLFOX (leucovorin calcium, 5-Fluorouracil, and oxaliplatin)
• Carboplatin
• Paclitaxel
• Radiation therapy

This research study involves the following study intervention:

- Liposomal irinotecan

It is expected that about 40 people will take part in this research study.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The U.S. Food and Drug Administration (FDA) has not approved liposomal irinotecan for your specific disease but it has been approved for other uses. The FDA has approved FOLFOX, carboplatin, and paclitaxel as treatment options for this disease.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Theodore S Hong, MD; Phone Number: (617) 726-6050; Email: tshong1@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Theodore R. Hong, MD; Phone Number: 617-726-6050; Email: tshong1@mgh.harvard.edu
      • Principal Investigator: Theodore R Hong, MD
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Beth-Israel Deaconess Medical Center
      • Principal Investigator: Andrea Bullock, MD
      • Contact: Andrea Bullock, MD; Phone Number: 617-667-2100; Email: abullock@bidmc.harvard.edu
    • Newton, Massachusetts, United States, 02462
      • Recruiting
      • Massachusetts General Hospital at Newton Wellesley Hospital
      • Contact: Lawrence Blaszkowsky, MD; Phone Number: 617-219-1230; Email: lblaszkowsky@partners.org
      • Principal Investigator: Lawrence Blaszkowsky, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must meet all the following criteria in order to be eligible to participate in the study:
• Histologically or cytologically confirmed T 3/4 or N+ (> 1 cm in size or FDG avid) Siewart 1-3 gastroesophageal (GE) junction or esophagogastric cancer. Diagnosis must be confirmed by a DF/HCC institution pathology department prior to registration.
• Age 18 years or older. There will be no upper age restriction.
• ECOG performance status ≤ 1
• Life expectancy of greater than 3 months

• Participants must have adequate organ and marrow function as defined below:

  • absolute neutrophil count ≥ 1,500 cells/mm3
  • platelets ≥ 75,000 cells/mm3
  • total bilirubin ≤ 1.5 x upper limit of normal OR for patients who have undergone biliary stenting, total bilirubin of ≤ 2.0 x upper limit of normal OR two down trending values.
  • AST(SGOT) ≤ 2.5 x upper limit of normal
  • ALT (SGPT) ≤ 2.5 x upper limit of normal
  • creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• The effects of both radiation therapy and the chemotherapy agents used in this trial are known to be teratogenic. Therefore, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation plus 30 days from the last date of study drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Female subject of childbearing potential should have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Participants who fulfill any of the following criteria will be excluded from the study:
• Evidence of metastatic disease as determined by chest CT scan, abdomen/pelvis CT scan (or MRI with gadolinium and/or manganese) within six weeks of study entry. Distant nodal disease is allowed if it is in the radiation port.
• Any prior chemotherapy, targeted/biologic therapy, or radiation for treatment of the participant's esophagogastric cancer.
• Treatment of other invasive carcinomas within the last five years with greater than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/ squamous cell carcinoma of the skin are allowed.
• Receipt of any other investigational agents within 4 weeks preceding the start of study treatment.
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity (e.g.congestive heart failure, symptomatic coronary artery disease and/or cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, or ongoing infection as manifested by fever.
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or drug intake.
• Pregnant women are excluded from this study because radiation therapy and the chemotherapy agents to be used have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the mother is receiving protocol therapy.
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery.
• No concurrent administration of cimetidine (as it can decrease the clearance of 5-FU). Another H2-blocker or proton pump inhibitor may be substituted before study entry.
• Known, existing uncontrolled coagulopathy.
• Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and at least six months earlier). Prior topical fluoropyrimidine use is allowed.
• Known hypersensitivity to 5-fluorouracil or known DPD deficiency.
• History of allergic reaction(s) attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, irinotecan, or oxaliplatin.

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: FOLFOX/ nal-IRI; Treatment will be administered on an outpatient basis.; FOLFOX with nal-IRI for eight two-week cycles (16 weeks total); Chemoradiation with proton or photon radiation therapy concurrent with weekly Paclitaxel and Carboplatin for 5 weeks; Surgery

Drug: FOLFOX/ nal-IRI; A cycle will be two weeks (14 days) long, with FOLFOX/ nal-IRI administered on days 1-3. The order of FOLFOX/ nal-IRI administration is as follows: 1) Liposomal Irinotecan free base via IV, predetermined dosage per protocol; 2) Oxaliplatin via IV, predetermined dosage per protocol; 3) Leucovorin via IV, predetermined dosage per protocol; 4) 5-Fluorouracil via IV, predetermined dosage per protocol; Drug: Paclitaxel; Paclitaxel and Carboplatin will be given concurrently with radiation therapy weekly (+/- 1 day).; Other Names: Abraxane®.; Drug: Carboplatin; Paclitaxel and Carboplatin will be given concurrently with radiation therapy weekly (+/- 1 day).; Other Names: Paraplatin; Radiation: Proton Radiation Therapy; Chemoradiation with proton or photon radiation therapy concurrent with weekly Paclitaxel and Carboplatin for 5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate	All patients will undergo a full pathological review of their surgical specimen according to the AJCC Staging Classification, 6th. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.	38 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0	Toxicity associated with neoadjuvant FOLFOX/ nal-IRI and chemoradiation will be summarized by category and grade according to the CTCAE version 5.0 Acute and late toxicities will be scored using Common Toxicity Criteria (CTCAE) version 5. Toxicities will be noted and recorded in protocol-specific case reports from the time of first dose of protocol therapy until 5 years after the end of protocol therapy	first dose of protocol therapy until 5 years after the end of protocol therapy
Clinical Response	The rate of objective clinical response to induction FOLFOX/ nal-IRI and chemoradiation will be reported as the proportion of eligible patients starting protocol therapy who achieve a complete or partial response as the best overall response	8 Weeks
Clinical Response	The rate of objective clinical response to induction FOLFOX/ nal-IRI and chemoradiation will be reported as the proportion of eligible patients starting protocol therapy who achieve a complete or partial response as the best overall response	16 Weeks
Clinical Response	The rate of objective clinical response to induction FOLFOX/ nal-IRI and chemoradiation will be reported as the proportion of eligible patients starting protocol therapy who achieve a complete or partial response as the best overall response	25 Weeks
Progression-Free Survival (PFS)	Progression-free survival (PFS) is defined as the duration from the first date of protocol therapy to the earliest date of disease progression per RECIST criteria or death due to any cause. PFS time will be censored at the date of last follow-up for patients still alive with no documentation of progressive disease. The PFS rate will be estimated using the Kaplan-Meier method with 95% confidence intervals based on the complementary log-log transformation.	duration from the first date of protocol therapy to the earliest date of disease progression up 5 years
Overall Survival	Overall survival (OS) is defined as the duration from the first date of protocol therapy to the date of death due to any cause and will be censored at the date of last follow-up for patients still alive. The OS rate will be estimated using the Kaplan-Meier method with 95% confidence intervals based on the complementary log-log transformation	first date of protocol therapy to the date of death due to any cause and will be censored at the date of last follow-up for patients still alive up to 5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Gastroesophageal Junction Adenocarcinoma; Esophagogastric cancer
• 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; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: 20-452

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes