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

This study is not yet open for participant recruitment.
Verified October 2013 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01928290
First received: August 19, 2013
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Stomach Neoplasms
Esophageal Neoplasms
Drug: Irinotecan
Drug: Trastuzumab
Drug: Oxaliplatin
Drug: Leucovorin
Drug: Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of FOLFIRINOX Chemotherapy for Treatment of Advanced Gastric, Gastro-esophageal Junction, and Esophageal Tumors

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Objective response rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Objective response rate (defined as CR + PR by RECIST 1.1 criteria)


Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Duration of time from start of treatment to time of progression or death, whichever occurs first.

  • Time to progression (TTP) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    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.

  • Overall survival (OS) [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Overall survival is defined as the time interval from date of diagnosis to date of death from any cause.

  • Clinical benefit rate [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    Clinical benefit rate is the percentage of combined patients who have achieved complete response (CR), partial response (PR), and stable disease (SD).

  • Duration of Response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    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

  • Toxicity and tolerability [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    NCI CTCAE v. 4.0 toxicity Grade 3 and Grade 4 laboratory abnormalities will be listed.


Estimated Enrollment: 41
Study Start Date: December 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRINOX

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.

Flurorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.

Drug: Irinotecan
Other Names:
  • Irinotecan
  • 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
  • Fluorouracil
  • Adrucil® Injection
  • 5-Fluorouracil
  • 5-FU
Experimental: FOLFIRINOX and Trastuzumab

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.

Flurorouracil 400 mg/m2 bolus and 2400 mg/m2 CIVI over 46 hours beginning on Day 1 and Day 15.

Drug: Irinotecan
Other Names:
  • Irinotecan
  • 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
  • Fluorouracil
  • Adrucil® Injection
  • 5-Fluorouracil
  • 5-FU

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 within normal institutional limits 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. History of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01928290

Contacts
Contact: A. Craig Lockhart, M.D. 314-362-5740 alockhar@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Not yet recruiting
St. Louis, Missouri, United States, 63110
Contact: A. Craig Lockhart, M.D.         
Sub-Investigator: Seth Crosby, M.D.         
Sub-Investigator: Christopher Maher, Ph.D.         
Sub-Investigator: Joel Picus, M.D.         
Sub-Investigator: Robert Pufahl, Ph.D.         
Sub-Investigator: Caron Rigden, M.D.         
Sub-Investigator: Anna Roshal, M.D.         
Sub-Investigator: Steven Sorscher, M.D.         
Sub-Investigator: Rama Suresh, M.D.         
Sub-Investigator: Benjamin Tan, M.D.         
Sub-Investigator: Andrea Wang-Gillam, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: A. Craig Lockhart, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01928290     History of Changes
Other Study ID Numbers: 201309035
Study First Received: August 19, 2013
Last Updated: October 30, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Esophageal Neoplasms
Neoplasms
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Trastuzumab
Formyltetrahydrofolates
Leucovorin
Tetrahydrofolates
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on April 17, 2014