Neoplasms

All Conditions

Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Fluorouracil

Oxaliplatin

Lapatinib

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery

5-Fluorouracil

Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.

Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion

Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6

Radiation Therapy

Johanna C Bendell, MD

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.

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

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

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.

An additional primary objective is to evaluate the safety and optimal dose of lapatinib when added to 5-FU, oxaliplatin and radiation therapy.

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.

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.

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.

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

GlaxoSmithKline

SCRI Development Innovations, LLC

Combined Modality Treatment of Radiation therapy, 5-Fluorouracil, Oxaliplatin and Lapatinib followed by Surgery

5-Fluorouracil: 5-FU, 225 mg/m2 IVCI, during XRT.

Oxaliplatin: Oxaliplatin, 85 mg/m2 IV, Days 1, 15, 29.

Lapatinib: Lapatinib, Continuous PO daily dosing during XRT, dose determined during lead in portion

Radiation Therapy: Radiation therapy, 50.4 Gy (1.8 Gy/day or 28 fractions) M-F, Weeks1-6

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer	NCT01769508	HER2 Positive E...	5-Fluorouracil Oxaliplatin Lapatinib Radiation Thera...	18 Years -	SCRI Development Innovations, LLC
Study of 5-FU, Oxaliplatin, & Lapatinib Combined With Radiation Therapy to Treat HER2 Positive Esophagogastric Cancer	NCT01769508	HER2 Positive E...	5-Fluorouracil Oxaliplatin Lapatinib Radiation Thera...	18 Years -	SCRI Development Innovations, LLC

Spots Global Cancer Trial Database for her2 positive esophagogastric cancer