Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01769508
Recruitment Status : Terminated (Study closed due to slow accrual.)
First Posted : January 16, 2013
Results First Posted : April 27, 2016
Last Update Posted : June 13, 2016
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
With improvements in response rate and survival seen for HER2 positive patients treated with HER2 blockade in the metastatic setting, the use of HER2 blockade in the neoadjuvant setting to increase antitumor effect shows promise. Patients with previously untreated localized HER2 positive esophageal, GE junction and gastric adenocarcinomas will be enrolled. Patients meeting all inclusion/exclusion criteria will receive neoadjuvant treatment with concurrent chemotherapy and radiation therapy beginning on day 1 of treatment. During the lead-in safety portion, the optimal dose of lapatinib will be determined.

Condition or disease Intervention/treatment Phase
HER2 Positive Esophagogastric Cancer Drug: 5-Fluorouracil Drug: Oxaliplatin Drug: Lapatinib Radiation: Radiation Therapy Phase 2

Detailed Description:

This is an open-label, non-randomized, Phase II study with a lead-in safety cohort. The study will evaluate the combination of 5-Fluorouracil, Oxaliplatin and Lapatinib with radiation therapy as neoadjuvant treatment for patients with previously untreated localized HER2 positive esophagogastric adenocarcinomas. Approximately 12 patients will be enrolled in the lead-in cohort to evaluate the safety of the combination. Following the lead-in cohort, Phase II will commence and up to 30 additional patients may be treated. The starting doses will be administered as follows:

5-FU 225 mg/mg2 continuous intravenous (IV) infusion Days 1 - 42 during XRT; Oxaliplatin 85 mg/m2 Days 1, 15 and 29, given by IV infusion, per institutional standard; Lapatinib Continuous PO daily dosing during XRT (final dose determined during lead-in cohort).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study With Lead-in Safety Cohort of 5-Fluorouracil, Oxaliplatin and Lapatinib in Combination With Radiation Therapy as Neoadjuvant Treatment for Patients With Localized HER2 Positive Esophagogastric Adenocarcinomas
Study Start Date : February 2013
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Combined Therapy
Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery
Drug: 5-Fluorouracil
5-FU, 225 mg/m2 IVCI, during XRT.
Other Name: Combined Modality Treatment
Drug: Oxaliplatin
Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.
Other Name: Combined Modality Treatment
Drug: Lapatinib
Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion
Other Name: Combined Modality Treatment
Radiation: Radiation Therapy
Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6

Primary Outcome Measures :
  1. Pathologic Complete Response Rate (pCR Rate) [ Time Frame: 18 months ]
    Defined as the absence of invasive tumor in esophagogastric and lymph node tissue removed at time of surgery, as judged by the local pathologist. An improvement in pCR rate from 30 percent (historical) to 50 percent is the primary efficacy endpoint.

  2. Safety and Optimal Dose of Regimen [ Time Frame: 18 months ]
    An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 18 months ]
    The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  2. Toxicity Profile for Treated Patients [ Time Frame: 18 months ]
    Defined as the frequency of adverse events for patients who received at least one dose of study treatment, and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.

  3. Time to Progression (TTP) [ Time Frame: 18 months ]
    Time to progression is defined as the time between day 1 cycle 1 and time to first documented disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  4. Overall Survival (OS) [ Time Frame: 18 months ]
    The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Histologically confirmed Stage I, II, or III adenocarcinoma of the esophagus (lower ⅓), GE junction, or gastric cardia.
  • Clinical stage I, II, or III as assessed by required baseline staging. In addition, patients with celiac node involvement (stage IVa) are eligible.
  • Patients must be surgical candidates based on stage and location of disease as well as other medical conditions and risk factors.
  • Positive HER2 status (overexpression and/or amplification of HER2 in primary tumor) as defined by FISH (HER2 FISH positivity).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
  • Patient must be able to swallow and absorb oral medication.
  • Patients must have an indwelling central venous access catheter.
  • Adequate hematologic, renal, and hepatic function:
  • Known brain or leptomeningeal metastases.
  • Male patients willing to use adequate contraceptive measures.
  • Female patients who are not of child-bearing potential, and female patients of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of treatment.
  • Life expectancy ≥ 12 weeks.
  • Age ≥18 years of age.
  • Willingness and ability to comply with trial and follow-up procedures.
  • Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria:

  • Patients with evidence of distant metastases are ineligible, as are patients who are not potential surgical candidates based on location or extent of local disease. Patients with celiac nodal disease (Stage IVa) will be allowed on study.
  • Previous anti-cancer treatment for esophageal, GE junction, or gastric cancer.
  • Any other investigational agents within the 28 days prior to day 1 of the study.
  • Known active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
  • Concurrent treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A that cannot be discontinued or switched to different medication prior to starting study drug.
  • Concurrent use of St. John's wort and grapefruit /grapefruit juice ≤7 days prior to starting study drug is not allowed.
  • Ongoing treatment with full-dose warfarin or its equivalent. Prophylactic treatment with 1 mg daily of warfarin and/or low molecular weight heparin is allowed.
  • History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of a novel regimen, or that might affect interpretation of the results of this study or render the subject at high-risk for treatment complications.
  • Active gastrointestinal (GI) disease or other condition that in the opinion of the investigator will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, or vomiting).
  • Poorly controlled or clinically significant atherosclerotic vascular disease
  • A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  • Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).
  • Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  • Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01769508

United States, Florida
Florida Cancer Specialists - South
Fort Myers, Florida, United States, 33916
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
Woodlands Medical Specialists
Pensacola, Florida, United States, 32503
Florida Cancer Specialists-North
St. Petersburg, Florida, United States, 33705
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Michigan
Grand Rapids Oncology Program
Grand Rapids, Michigan, United States, 49503
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Chattanooga Oncology and Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Study Chair: Johanna C Bendell, MD SCRI Development Innovations, LLC

Responsible Party: SCRI Development Innovations, LLC Identifier: NCT01769508     History of Changes
Other Study ID Numbers: SCRI GI 166
First Posted: January 16, 2013    Key Record Dates
Results First Posted: April 27, 2016
Last Update Posted: June 13, 2016
Last Verified: May 2016

Keywords provided by SCRI Development Innovations, LLC:
Esophagogastric Adenocarcinoma
Radiation Therapy

Additional relevant MeSH terms:
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors