Clinical trial NCT04656041: Folfox+Irinotecan+Chemort In Esophageal Cancer
Official title: A Phase II Study of Neoadjuvant NAPOX Followed by Chemoradiation With Paclitaxel and Carboplatin in Locally Advanced Esophagogastric Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastroesophageal Junction Adenocarcinoma
Esophagogastric Cancer
Keywords: Gastroesophageal Junction Adenocarcinoma
Esophagogastric cancer
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2020-12-07
Enrollment: 40
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: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: 38 Weeks
Secondary outcomes:
measure: Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: first dose of protocol therapy until 5 years after the end of protocol therapy
measure: Clinical Response
timeFrame: 8 Weeks
measure: Clinical Response
timeFrame: 16 Weeks
measure: Clinical Response
timeFrame: 25 Weeks
measure: Progression-Free Survival (PFS)
timeFrame: duration from the first date of protocol therapy to the earliest date of disease progression up 5 years
measure: Overall Survival
timeFrame: 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
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth-Israel Deaconess Medical Center
state: Massachusetts
city: Newton
country: United States
facility: Massachusetts General Hospital at Newton Wellesley Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Theodore S Hong, MD
role: PRINCIPAL_INVESTIGATOR
References: