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

NCT01928290 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201309035
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Objective Response

  * 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.

  Through completion of treatment (estimated to be 4 months)

Secondary Outcomes (6)

• Progression Free Survival

  Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

• Time to Progression (TTP)

  Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

• Overall Survival (OS)

  Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

• Clinical Benefit Rate

  Through completion of treatment (estimated to be 4 months)

• Duration of Response

  Through 1 year after completion of treatment (median follow-up 16.2 months - 95% CI 4.7-42.5 months)

Study Arms (2)

Arm A: FOLFIRINOX (HER2-negative)

EXPERIMENTAL

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; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

EXPERIMENTAL

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; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Interventions

Irinotecan DRUG

Also known as: Camptosar®, CPT-11

Arm A: FOLFIRINOX (HER2-negative); Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Trastuzumab DRUG

Also known as: Herceptin®

Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Oxaliplatin DRUG

Also known as: Eloxatin®

Arm A: FOLFIRINOX (HER2-negative); Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Leucovorin DRUG

Also known as: Wellcovorin® I.V., citrovorum factor

Arm A: FOLFIRINOX (HER2-negative); Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Fluorouracil DRUG

Also known as: folinic acid, 5-formyl tetrahydrofolate, Adrucil® Injection, 5-Fluorouracil, 5-FU

Arm A: FOLFIRINOX (HER2-negative); Arm B: FOLFIRINOX & Trastuzumab (HER2-positive)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven and inoperable locally advanced, recurrent, or metastatic cancer of the esophagus, stomach, or gastro-esophageal junction.
• 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.
• Prior single modality radiation therapy is allowed.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcl
• Platelets ≥ 100,000/mcl
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
• Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• LVEF ≥ 50%
• 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.
• Ability to understand and willingness to sign an IRB approved written informed consent document (legally authorized representative is allowed).

You may not qualify if:

• Chemotherapy in the 6 months prior to registration.
• 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)
• Receiving any other investigational agents at the time of registration.
• 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.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
• Previous therapy for metastatic gastroesophageal cancer. Previous perioperative chemotherapy is allowed as long as the duration without treatment has been greater than 6 months..
• A history of congestive heart failure, transmural myocardial infarction, symptomatic valvular disease, or high-risk arrhythmia.
• 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.
• Pregnant and/or breastfeeding. Patient must have a negative urine pregnancy test within 14 days of study entry.
• 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.
• Both men and women and members of all races and ethnic groups are eligible for this trial.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 32469386 DERIVED

Related Links

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

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Interventions

Irinotecan; Trastuzumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Haeseong Park, M.D.
• Organization: Washington University School of Medicine

haeseongpark@wustl.edu

314-747-6268

Study Officials

• Haeseong Park, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2013
• First Posted: August 23, 2013
• Study Start: November 8, 2013
• Primary Completion: December 3, 2018
• Study Completion: October 28, 2019
• Last Updated: August 25, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)