Oxaliplatin, Fluorouracil, Erlotinib Hydrochloride, and Radiation Therapy Before Surgery and Erlotinib Hydrochloride After Surgery in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

NCT01561014 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB00007063NCI-2009-01447CCCWFU 60106
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with oxaliplatin, fluorouracil, and radiation before surgery and alone after surgery in treating patients with locally advanced cancer of the esophagus and gastroesophageal junction. Drugs used in chemotherapy, such as oxaliplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with erlotinib hydrochloride and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving erlotinib hydrochloride after surgery may kill any tumor cells that remain after surgery

Conditions

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage II Esophageal Cancer; Stage II Gastric Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride

  Toxicity will be determined using the revised National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0 for Toxicity and Adverse Event Reporting (CTCAE v3.0). The dose limiting toxicity will be defined as any of the following that can be attributal to therapy: Any grade 4 neutropenia and or any grade 4 thrombocytopenia, or any \>= grade 3 non-hematologic toxicity that results in a greater than 3 day interruption of therapy.

  Approximately 6 months

Secondary Outcomes (5)

• Time to progression

  Approximately 4 years

• Survival

  Approximately 4 years

• Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)

  Over 4 years

• Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression)

  Approximately 1 year

• Test the predictive value of FDG-PET-CT imaging in identifying patients who will have a complete response

  Approximately 1 year

Study Arms (1)

Treatment (chemotherapy, enzyme inhibitor therapy)

EXPERIMENTAL

CHEMORADIOTHERAPY: Patients undergo radiation therapy QD, 5 days a week and receive fluorouracil IV continuously and erlotinib hydrochloride PO QD on days 1-38. Patients also receive oxaliplatin IV over 2 hours on days 1, 15, and 29. SURGERY: Within 4-8 weeks after completion of chemoradiotherapy, patients with potentially resectable disease (i.e., complete response, partial response, or stable disease) undergo surgery to remove the tumor. CONSOLIDATION CHEMOTHERAPY: Within 2-4 weeks after surgery, patients with tumors that demonstrate positive immunohistochemistry for EGFR and/or cyclin D1 (in the pretreatment biopsy or in the residual tumor in the esophagectomy specimen) receive consolidation chemotherapy comprising erlotinib hydrochloride PO QD for 12 weeks.

Drug: erlotinib hydrochloride; Drug: oxaliplatin; Drug: fluorouracil; Radiation: radiation therapy; Procedure: conventional surgery; Other: immunohistochemistry staining method; Procedure: positron emission tomography; Procedure: computed tomography; Procedure: laboratory biomarker analysis; Genetic: gene expression analysis; Radiation: fludeoxyglucose F 18

Interventions

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Treatment (chemotherapy, enzyme inhibitor therapy)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (chemotherapy, enzyme inhibitor therapy)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (chemotherapy, enzyme inhibitor therapy)

radiation therapy RADIATION

Undergo radiotherapy

Also known as: irradiation, radiotherapy, therapy, radiation

Treatment (chemotherapy, enzyme inhibitor therapy)

conventional surgery PROCEDURE

Undergo surgical resection

Also known as: surgery, conventional

Treatment (chemotherapy, enzyme inhibitor therapy)

immunohistochemistry staining method OTHER

Correlative study

Also known as: immunohistochemistry

Treatment (chemotherapy, enzyme inhibitor therapy)

positron emission tomography PROCEDURE

Correlative study

Also known as: FDG-PET, PET, PET scan, tomography, emission computed

Treatment (chemotherapy, enzyme inhibitor therapy)

computed tomography PROCEDURE

Correlative study

Also known as: tomography, computed

Treatment (chemotherapy, enzyme inhibitor therapy)

laboratory biomarker analysis PROCEDURE

Correlative study

Treatment (chemotherapy, enzyme inhibitor therapy)

gene expression analysis GENETIC

Correlative study

Treatment (chemotherapy, enzyme inhibitor therapy)

fludeoxyglucose F 18 RADIATION

Undergo F18 PET and CT scan

Also known as: 18FDG, FDG

Treatment (chemotherapy, enzyme inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed patients with locally advanced esophageal cancer with either squamous or adenocarcinoma histology; patients should have evidence of extension of disease into or through the wall of the esophagus (T2-4) and/or regional nodal metastasis (N1)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Non-pregnant; patients of childbearing potential and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method); nursing mothers are also ineligible
• Prior treatment: Greater than one week shall have elapsed since any major surgery; no prior chemotherapy or radiotherapy is allowed
• Adequate whole blood cell (WBC) and platelets (Plt) as determined by medical oncology
• Serum creatinine =\< 1.5 mg/dl
• Creatinine clearance \>= 60 ml/min
• Hemoglobin (Hgb) \>= 9.0 gm/dl
• Absolute neutrophil count \>= 1,500/uL
• Serum total bilirubin =\< 1.5 mg/dL
• Alkaline phosphatase =\< 3X the upper limit of normal (ULN) for the reference lab
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 2X ULN for the reference laboratory
• Patients must be told of the investigational nature of the study and must sign a written informed consent
• No serious medical or psychiatric illnesses which would prevent informed consent or otherwise limit survival to less than two years; no history of refractory congestive heart failure or cardiomyopathy
• Patients should be evaluated by medical oncology, radiation oncology, and surgery, and felt to by all to be suitable for trimodality therapy

You may not qualify if:

• Patients with an active infection or with a fever \>= 38.5 degrees Celsius (C) within 3 days of the first scheduled day of protocol treatment
• History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate surface antigen (PSA) of \< 1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to entry
• Patients with known hypersensitivity to any of the components of oxaliplatin
• Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication)
• Peripheral neuropathy \>= Grade 2
• History of allogeneic transplant
• Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
• Pregnancy

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Stomach Neoplasms

Interventions

Erlotinib Hydrochloride; Oxaliplatin; Fluorouracil; Radiotherapy; Radiation; Surgical Procedures, Operative; Congresses as Topic; Immunohistochemistry; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Gene Expression Profiling; Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics; Physical Phenomena; Organizations; Health Care Economics and Organizations; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Genetic Techniques; Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Arthur Blackstock

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2012
• First Posted: March 22, 2012
• Study Start: April 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: July 2, 2018

Record last verified: 2018-06

Locations

US (1)