Combination Chemotherapy in Treating Patients With Advanced Stomach, Gastroesophageal, or Esophageal Cancer (FOLFIRINOX)

• ClinicalTrials.gov Identifier: NCT01928290
• Recruitment Status: Completed
• First Posted: August 23, 2013
• Results First Posted: January 18, 2020
• Last Update Posted: August 25, 2020
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

This phase II trial studies how well combination chemotherapy works in treating patients with advanced stomach, gastroesophageal, or esophageal cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Condition or disease	Intervention/treatment	Phase
Stomach Neoplasms; Esophageal Neoplasms	Drug: Irinotecan; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of FOLFIRINOX Chemotherapy for Treatment of Advanced Gastric, Gastro-esophageal Junction, and Esophageal Tumors
• Actual Study Start Date: November 8, 2013
• Actual Primary Completion Date: December 3, 2018
• Actual Study Completion Date: October 28, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: FOLFIRINOX (HER2-negative); Irinotecan 180 mg/m2 IV on Days 1 & 15. Oxaliplatin 85 mg/m2 IV on Days 1 & 15. Leucovorin 400 mg/m2 IV on Days 1 & 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Drug: Irinotecan; Other Names: Camptosar®; CPT-11; Drug: Oxaliplatin; Other Name: Eloxatin®; Drug: Leucovorin; Other Names: Wellcovorin® I.V.; citrovorum factor; Drug: Fluorouracil; Other Names: folinic acid; 5-formyl tetrahydrofolate; Adrucil® Injection; 5-Fluorouracil; 5-FU
Experimental: Arm B: FOLFIRINOX & Trastuzumab (HER2-positive); Trastuzumab 8 mg/kg on Cycle 1 Day 1 then 4 mg/kg on Day 15 and Day 1 of all future cycles. Irinotecan 180 mg/m2 IV on Days 1 & 15. Oxaliplatin 85 mg/m2 IV on Days 1 & 15. Leucovorin 400 mg/m2 IV on Days 1 & 15. Fluorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.	Drug: Irinotecan; Other Names: Camptosar®; CPT-11; Drug: Trastuzumab; Other Name: Herceptin®; Drug: Oxaliplatin; Other Name: Eloxatin®; Drug: Leucovorin; Other Names: Wellcovorin® I.V.; citrovorum factor; Drug: Fluorouracil; Other Names: folinic acid; 5-formyl tetrahydrofolate; Adrucil® Injection; 5-Fluorouracil; 5-FU

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With an Objective Response [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
   • Objective response (defined as complete response (CR) + partial response (PR) by RECIST 1.1 criteria)
   • CR: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
   • PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures :

1. Progression Free Survival [ Time Frame: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months) ]
   Duration of time from start of treatment to time of progression or death, whichever occurs first.
2. Time to Progression (TTP) [ Time Frame: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months) ]
   Duration of time from start of treatment to time of progression. Progression is defined as 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.
3. Overall Survival (OS) [ Time Frame: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months) ]
   Overall survival is defined as the time interval from date of diagnosis to date of death from any cause.
4. Clinical Benefit Rate [ Time Frame: Through completion of treatment (estimated to be 4 months) ]
   • Clinical benefit rate is the percentage of combined patients who have achieved complete response (CR), partial response (PR), and stable disease (SD)
   • CR: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm
   • PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
   • SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
5. Duration of Response [ Time Frame: Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months) ]
   Time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented
6. Toxicity and Tolerability (Arm A and Arm B) as Measured by the Number of Participants With Grade 3 or Higher Adverse Events [ Time Frame: 30 days after completion of treatment (estimated to be 5 months) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Biopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction.
2. Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam.
3. Prior single modality radiation therapy is allowed.
4. At least 18 years of age.
5. ECOG performance status ≤ 2

6. Normal bone marrow and organ function as defined below:

   1. Absolute neutrophil count ≥ 1,500/mcl
   2. Platelets ≥ 100,000/mcl
   3. AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
   4. Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
   5. LVEF ≥ 50%
7. Women of childbearing 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
8. Ability to understand and willingness to sign an IRB approved written informed consent document (legally authorized representative is allowed).
9. Patients already receiving treatment with FOLFIRINOX +/- trastuzumab may participate in the study and have their data collected retrospectively if they met inclusion criteria at the start of therapy and sign consent for study participation moving forward.

Exclusion Criteria:

1. Chemotherapy in the 6 months prior to registration.
2. Any active malignancy within 3 years that may alter the course of esophageal cancer (Apparently cured localized malignancy or advanced, but indolent malignancy with significantly more favorable prognosis are allowed)
3. Receiving any other investigational agents at the time of registration.
4. Known untreated brain metastases. These patients must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
5. A history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
6. Previous therapy for metastatic gastroesophageal cancer. Previous perioperative chemotherapy is allowed as long as the duration without treatment has been greater than 6 months..
7. A history of congestive heart failure, transmural myocardial infarction, symptomatic valvular disease, or high-risk arrhythmia.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within 14 days of study entry.
10. Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with trastuzumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.

Inclusion of Women and Minorities

Both men and women and members of all races and ethnic groups are eligible for this trial.

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Haeseong Park, M.D.; Washington University School of Medicine

  Study Documents (Full-Text)

Documents provided by Washington University School of Medicine:

Study Protocol and Statistical Analysis Plan  [PDF] December 21, 2017

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Park H, Jin RU, Wang-Gillam A, Suresh R, Rigden C, Amin M, Tan BR, Pedersen KS, Lim KH, Trikalinos NA, Acharya A, Copsey ML, Navo KA, Morton AE, Gao F, Lockhart AC. FOLFIRINOX for the Treatment of Advanced Gastroesophageal Cancers: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2020 Aug 1;6(8):1231-1240. doi: 10.1001/jamaoncol.2020.2020.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01928290
• Other Study ID Numbers: 201309035
• First Posted: August 23, 2013
• Results First Posted: January 18, 2020
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Leucovorin; Formyltetrahydrofolates; Tetrahydrofolates; Fluorouracil; Oxaliplatin; Trastuzumab; Irinotecan; Levoleucovorin; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors