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CompletedNCT03279237Updated May 18, 2026Results posted

A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers

A Phase 1 interventional study of Irinotecan and Oxaliplatin in GastroEsophageal Cancer, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-18.

Sponsored by Massachusetts General Hospital · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This research study is studying a combination of interventions as a possible treatment for gastroesophageal (GE) junction cancer.

The interventions involved in this study are:

-FOLFIRINOX which is made up of 4 different drugs:

  • 5-Fluorouracil (5-FU)
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • Paclitaxel
  • Carboplatin
  • Proton Beam Radiation Therapy
Read the detailed description

This research study is a Pilot Study, which is the first time investigators are examining this study intervention.

In this research study, the investigators are studying the combination of FOLFIRINOX followed by radiation with paclitaxel and carboplatin before surgery. The investigators believe that this intervention may help decrease the growth and spread of the cancer cells.

FOLFIRINOX has shown to be very effective in patients whom disease has spread. The investigators are evaluating this regimen to see if there is an increase in curability when the cancer has not spread.

The FDA (the U.S. Food and Drug Administration) has approved FOLFIRINOX as a treatment option for this disease.

The FDA has not approved Paclitaxel or Carboplatin for this specific disease but they have both been approved for other uses.

FOLFIRINOX is a combination of 4 chemotherapy agents that may help shrink the tumor before surgery.

Carboplatin may stop the cancer cells from growing and paclitaxel may stop the cancer cells from growing and spreading

02

Conditions studied

  • GastroEsophageal Cancer

Keywords

  • GastroEsophageal Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histologically or cytologically confirmed T 3/4 or N+ (> 1 cm in size or FDG avid) gastric or gastroesophageal (GE) junction cancer. Diagnosis must be confirmed by the Mass General Hospital pathology department.
  • 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 or two down trending values.
    • AST(SGOT) ≤ 2.5 × 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.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

Exclusion Criteria:

  • 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 gastric or GE junction cancer.
  • Receipt of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • 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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    FOLFIRINOX + pre-operative radiation

    * FOLFIRINOX is a combination of 4 drugs that is administered twice per cycle * Oxaliplatin is administered intravenously * Leucovorin is administered intravenously * Irinotecan is administered intravenously * 5-Fluorouracil is administered intravenously * Paclitaxel and Carboplatin will be given concurrently with radiation therapy every 7 days

    Drug: Irinotecan · Drug: Oxaliplatin · Drug: Leucovorin · Drug: 5-Fluorouracil · Drug: Paclitaxel · Radiation: Radiation Therapy · Drug: Carboplatin

Interventions

  • DrugIrinotecan

    May help shrink tumor before surgery.

    Also known as: Camptosar

  • DrugOxaliplatin

    May help shrink tumor before surgery.

    Also known as: Eloxatin

  • DrugLeucovorin

    May help shrink tumor before surgery.

  • Drug5-Fluorouracil

    May help shrink tumor before surgery.

    Also known as: Efudex

  • DrugPaclitaxel

    Paclitaxel may stop cancer cells from growing and spreading.

    Also known as: Abraxane

  • RadiationRadiation Therapy

    May help shrink tumor.

  • DrugCarboplatin

    Carboplatin may stop cancer cells from growing.

05

What researchers measure

Primary outcomes

  1. The Completion Rate of Chemotherapy in Combination With Chemoradiation

    The number of participants that complete the assigned study intervention.

    Time frame: 21 weeks

Secondary outcomes

  1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

    The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).

    Time frame: From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)

  2. Clinical Response Rate

    The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Time frame: After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)

  3. Pathologic Complete Response Rate

    The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. 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.

    Time frame: 29 Weeks

  4. Progression Free Survival

    Progression-free survival (PFS) is defined as the time from the date of first dosing to the first documentation of radiographic disease progression per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Subjects who are alive with no documented progressive disease by the data cutoff date for PFS analysis will be censored at the date of their last evaluable disease assessment. Progressive Disease (PD) is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    Time frame: 5 Years

  5. Overall Survival

    The number of participants alive five years after the start of treatment. Overall survival (OS) is measured as the time from the date of first dosing until death due to any cause. If there is no death reported for a subject by the data cut-off date for overall survival analysis, OS will be censored at the last known alive date.

    Time frame: 5 Years

06

Results

Posted May 7, 2020

Participant flow

Participant flow — Overall Study
MilestoneFOLFIRINOX + Pre-operative Radiation
Started25
Chemo-radiation23
Surgical resection20
Completed20
Not completed5

Outcome measures

PrimaryThe Completion Rate of Chemotherapy in Combination With Chemoradiation

The number of participants that complete the assigned study intervention.

Time frame:
21 weeks
Reported as:
Count of participants · Participants
The Completion Rate of Chemotherapy in Combination With Chemoradiation
ParticipantsFOLFIRINOX + Pre-operative Radiation
The Completion Rate of Chemotherapy in Combination With Chemoradiation23
SecondaryNumber of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

The number of participants that experienced at least one treatment related adverse event as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Time frame:
From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
ParticipantsFOLFIRINOX + Pre-operative Radiation
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.025
SecondaryClinical Response Rate

The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time frame:
After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)
Reported as:
Count of participants · Participants
Clinical Response Rate
ParticipantsFOLFIRINOX + Pre-operative Radiation
Clinical Response Rate20
SecondaryPathologic Complete Response Rate

The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. 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.

Time frame:
29 Weeks
Reported as:
Count of participants · Participants
Pathologic Complete Response Rate
ParticipantsFOLFIRINOX + Pre-operative Radiation
Pathologic Complete Response Rate7
SecondaryProgression Free Survival

Progression-free survival (PFS) is defined as the time from the date of first dosing to the first documentation of radiographic disease progression per Response Evaluation Criteria In Solid Tumors (RECIST v1.1) or death due to any cause, whichever occurs first. Subjects who are alive with no documented progressive disease by the data cutoff date for PFS analysis will be censored at the date of their last evaluable disease assessment. Progressive Disease (PD) is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Time frame:
5 Years

Results for this outcome have not been posted.

SecondaryOverall Survival

The number of participants alive five years after the start of treatment. Overall survival (OS) is measured as the time from the date of first dosing until death due to any cause. If there is no death reported for a subject by the data cut-off date for overall survival analysis, OS will be censored at the last known alive date.

Time frame:
5 Years

Results for this outcome have not been posted.

Adverse events

Collected over From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
FOLFIRINOX + Pre-operative Radiation1/25 (4%)24/25 (96%)—
Most frequent serious events
Showing 10 of 20
Most frequent serious events
EventFOLFIRINOX + Pre-operative Radiation
Lymphopenia/Leukopenia/NeutropeniaBlood and lymphatic system disorders21/25
Hypokalemia/Hyponatremia/HypocalcemiaMetabolism and nutrition disorders5/25
ThrombocytopeniaBlood and lymphatic system disorders4/25
Nausea/vomitingMetabolism and nutrition disorders4/25
DiarrheaMetabolism and nutrition disorders4/25
AnemiaBlood and lymphatic system disorders3/25
DehydrationMetabolism and nutrition disorders3/25
Febrile NeutropeniaBlood and lymphatic system disorders2/25
AnorexiaMetabolism and nutrition disorders2/25
InfectionMetabolism and nutrition disorders2/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)FOLFIRINOX + Pre-operative Radiation
Median60 (30 to 76)
Sex: Female, Male
Sex: Female, Male(Participants)FOLFIRINOX + Pre-operative Radiation
Female8
Male17
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)FOLFIRINOX + Pre-operative Radiation
Region of Enrollment
Region of Enrollment(participants)FOLFIRINOX + Pre-operative Radiation
United States25
07

Study locations

1 site
  • Massachusetts General Hospital
    Boston, Massachusetts 02214, United States
08

References and documents

Publications

  • Wo JY, Clark JW, Eyler CE, Mino-Kenudson M, Klempner SJ, Allen JN, Keane FK, Parikh AR, Roeland E, Drapek LC, Ryan DP, Corcoran RB, Van Seventer E, Fetter IJ, Shahzade HA, Khandekar MJ, Lanuti M, Morse CR, Heist RS, Ulysse CA, Christopher B, Baglini C, Yeap BY, Mullen JT, Hong TS. Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas. Clin Cancer Res. 2021 Dec 1;27(23):6343-6353. doi: 10.1158/1078-0432.CCR-21-0331. Epub 2021 Jul 30. PubMed 34330715 ↗

Study documents

  • Protocol and statistical analysis plan · Aug 14, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03279237
Lead sponsor
Massachusetts General Hospital
Collaborators
National Cancer Institute (NCI)
Responsible party
Jennifer Wo (Principal Investigator, Massachusetts General Hospital) — Principal investigator
First posted
Sep 12, 2017
Start date
Oct 24, 2017
Primary completion
Sep 26, 2018
Completion
Apr 1, 2026
Results posted
May 7, 2020
Last update
May 18, 2026

Study contacts

Jennifer Wo, MD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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