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

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03279237
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 25
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 68.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
GastroEsophageal Cancer	Drug: Irinotecan; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Paclitaxel; Radiation: Radiation Therapy; Drug: Carboplatin	Phase 1

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers
• Actual Study Start Date: Oct 24, 2017
• Actual Primary Completion Date: Nov 20, 2018
• Anticipated Study Completion Date: Jun 30, 2023

Arms and Interventions

Arm

Intervention/Treatment

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; May help shrink tumor before surgery.; Other Names: Camptosar ; Drug: Oxaliplatin; May help shrink tumor before surgery.; Other Names: Eloxatin ; Drug: Leucovorin; May help shrink tumor before surgery.; Drug: 5-Fluorouracil; May help shrink tumor before surgery.; Other Names: Efudex ; Drug: Paclitaxel; Paclitaxel may stop cancer cells from growing and spreading.; Other Names: Abraxane ; Radiation: Radiation Therapy; May help shrink tumor.; Drug: Carboplatin; Carboplatin may stop cancer cells from growing.

Outcome Measures

Primary Outcome Measures

1. The Completion Rate of Chemotherapy in Combination With Chemoradiation [21 weeks]

   The number of participants that complete the assigned study intervention.

Secondary Outcome Measures

1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)]

   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).

2. Clinical Response Rate [After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)]

   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.

3. Pathologic Complete Response Rate [29 Weeks]

   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.

4. Progression Free Survival [5 Years]

   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).

5. Overall Survival [5 Years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02214

Sponsors and Collaborators

• Massachusetts General Hospital
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Theodore S. Hong, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 14, 2019

More Information

Publications

None provided.

• Responsible Party: Theodore Sunki Hong, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03279237
• Other Study ID Numbers: 17-311; U19CA021239-37
• First Posted: Sep 12, 2017
• Last Update Posted: Jan 20, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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.: No
• Keywords provided by Theodore Sunki Hong, Principal Investigator, Massachusetts General Hospital: GastroEsophageal Cancer
• Additional relevant MeSH terms: Leucovorin; Paclitaxel; Carboplatin; Fluorouracil; Oxaliplatin; Irinotecan

Study Results

Participant Flow

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Period Title: Overall Study
STARTED	25
Chemo-radiation	23
Surgical Resection	20
COMPLETED	20
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	8 32%
Male	17 68%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	The Completion Rate of Chemotherapy in Combination With Chemoradiation
Description	The number of participants that complete the assigned study intervention.
Time Frame	21 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Measure Participants	25
Count of Participants [Participants]	23 92%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Measure Participants	25
Count of Participants [Participants]	25 100%

3. Secondary Outcome

Title	Clinical Response Rate
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Measure Participants	25
Count of Participants [Participants]	20 80%

4. Secondary Outcome

Title	Pathologic Complete Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
Measure Participants	25
Count of Participants [Participants]	7 28%

5. Secondary Outcome

Title	Progression Free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From the start of treatment until 30 days after the end of treatment (up to approximately 25 weeks)
Adverse Event Reporting Description	Serious adverse events were defined as grade 3 or greater adverse events that were deemed to be at least possibly, probably, or definitely related to treatment. Non-serious adverse events were not captured.
Arm/Group Title	FOLFIRINOX + Pre-operative Radiation
Arm/Group Description	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 Irinotecan: May help shrink tumor before surgery. Oxaliplatin: May help shrink tumor before surgery. Leucovorin: May help shrink tumor before surgery. 5-Fluorouracil: May help shrink tumor before surgery. Paclitaxel: Paclitaxel may stop cancer cells from growing and spreading. Radiation Therapy: May help shrink tumor. Carboplatin: Carboplatin may stop cancer cells from growing.
All Cause Mortality
	FOLFIRINOX + Pre-operative Radiation
	Affected / at Risk (%)	# Events
Total	1/25 (4%)
Serious Adverse Events
	FOLFIRINOX + Pre-operative Radiation
	Affected / at Risk (%)	# Events
Total	24/25 (96%)
Blood and lymphatic system disorders
Lymphopenia/Leukopenia/Neutropenia	21/25 (84%)
Febrile Neutropenia	2/25 (8%)
Thrombocytopenia	4/25 (16%)
Anemia	3/25 (12%)
Metabolism and nutrition disorders
Hypokalemia/Hyponatremia/Hypocalcemia	5/25 (20%)
Dehydration	3/25 (12%)
Anorexia	2/25 (8%)
Weight loss	1/25 (4%)
Nausea/vomiting	4/25 (16%)
Diarrhea	4/25 (16%)
Dysphagia	1/25 (4%)
Mucositis, Oral	1/25 (4%)
Gastrointestinal, Other	1/25 (4%)
Infection	2/25 (8%)
Hypotension	2/25 (8%)
Fatigue	1/25 (4%)
ALT/ALK phosphatase elevated	1/25 (4%)
Cardiac	1/25 (4%)
Acute kidney injury	1/25 (4%)
Aspiration	1/25 (4%)
Other (Not Including Serious) Adverse Events
	FOLFIRINOX + Pre-operative Radiation
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.