Trial record 1 of 5 for:    GI 166
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Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by SCRI Development Innovations, LLC
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01769508
First received: January 11, 2013
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
HER2 Positive Esophagogastric Cancer
Drug: 5-Fluorouracil
Drug: Oxaliplatin
Drug: Lapatinib
Radiation: Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Pathologic Complete Response Rate (pCR rate) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    This trial seeks to evaluate the pathological complete response (pCR) rate of the combination of lapatinib and chemoradiation as neoadjuvant treatment for patients with localized HER2 positive esophagogastric adenocarcinomas.

  • Safety and optimal dose of regimen [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    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:
  • Progression Free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Progression Free Survival will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.

  • Toxicity profile for neoadjuvant patients treated with 5-FU, Oxaliplatin, Lapatinib and radiation therapy [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The toxicity assessments will be performed at week 4, once during week 8-10 and at the end of the study.

  • Time to Progression (TTP) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Time to Progression will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.

  • Overall Survival (OS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Overall Survival will be evaluated for neoadjuvant patients treated with 5-FU, oxaliplatin, lapatinib and radiation therapy.


Estimated Enrollment: 42
Study Start Date: January 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769508

Contacts
Contact: Sarah Cannon Research Institute 1-877-691-7274 asksarah@scresearch.net

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

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01769508     History of Changes
Other Study ID Numbers: SCRI GI 166
Study First Received: January 11, 2013
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by SCRI Development Innovations, LLC:
Esophagogastric Adenocarcinoma
5-Fluorouracil
Oxaliplatin
Lapatinib
Radiation Therapy
Surgery

Additional relevant MeSH terms:
Fluorouracil
Lapatinib
Oxaliplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014