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
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| ClinicalTrials.gov Identifier: NCT01561014 |
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Recruitment Status :
Completed
First Posted : March 22, 2012
Last Update Posted : July 2, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | 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 | Phase 1 |
OBJECTIVES:
I. The primary aim of this phase I study is to evaluate the safety of multi-drug chemotherapy (with the addition of an anti-epidermal growth factor receptor [EGFR] agent erlotinib [erlotinib hydrochloride]) and concomitant radiotherapy followed by resection and consolidative erlotinib for the treatment of locally advanced esophageal cancer as judged by the dose limiting toxicities. Correlative endpoints include an analysis of pre-treatment tumor cyclin D1 expression and EGFR expression/amplification.
III. Correlate pathologic complete response with changes in fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)-computed tomography (CT) - pre and post-chemoradiation.
OUTLINE: This is a dose escalation study of erlotinib hydrochloride
CHEMORADIOTHERAPY: Patients undergo radiation therapy once daily (QD), 5 days a week and receive fluorouracil intravenously (IV) continuously and erlotinib hydrochloride orally (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.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 9 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Study of Preoperative Chemoradiation With Oxaliplatin, 5-Fluorouracil, Erlotinib and Radiation Followed by Resection and Consolidative Erlotinib for Patients With Locally Advanced Cancer of the Esophagus and Gastroesophageal Junction |
| Actual Study Start Date : | April 2007 |
| Actual Primary Completion Date : | March 2009 |
| Actual Study Completion Date : | March 2009 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (chemotherapy, enzyme inhibitor therapy)
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
Given PO
Other Names:
Drug: oxaliplatin Given IV
Other Names:
Drug: fluorouracil Given IV
Other Names:
Radiation: radiation therapy Undergo radiotherapy
Other Names:
Procedure: conventional surgery Undergo surgical resection
Other Name: surgery, conventional Other: immunohistochemistry staining method Correlative study
Other Name: immunohistochemistry Procedure: positron emission tomography Correlative study
Other Names:
Procedure: computed tomography Correlative study
Other Name: tomography, computed Procedure: laboratory biomarker analysis Correlative study Genetic: gene expression analysis Correlative study Radiation: fludeoxyglucose F 18 Undergo F18 PET and CT scan
Other Names:
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- Toxicity rate of combination chemotherapy followed by surgery and erlotinib hydrochloride [ Time Frame: Approximately 6 months ]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.
- Time to progression [ Time Frame: Approximately 4 years ]
- Survival [ Time Frame: Approximately 4 years ]
- Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression) [ Time Frame: Over 4 years ]
- Specific characteristics that predict complete response rate (e.g., EGFR status, EGFR amplification, and cyclin D1 expression) [ Time Frame: Approximately 1 year ]
- Test the predictive value of FDG-PET-CT imaging in identifying patients who will have a complete response [ Time Frame: Approximately 1 year ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
Exclusion Criteria:
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
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 ClinicalTrials.gov identifier (NCT number): NCT01561014
| United States, North Carolina | |
| Wake Forest University Health Sciences | |
| Winston-Salem, North Carolina, United States, 27157 | |
| Principal Investigator: | Arthur Blackstock | Wake Forest University Health Sciences |
| Responsible Party: | Wake Forest University Health Sciences |
| ClinicalTrials.gov Identifier: | NCT01561014 |
| Obsolete Identifiers: | NCT00499564 |
| Other Study ID Numbers: |
IRB00007063 NCI-2009-01447 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CCCWFU 60106 ( Other Identifier: Wake Forest University Health Sciences ) |
| First Posted: | March 22, 2012 Key Record Dates |
| Last Update Posted: | July 2, 2018 |
| Last Verified: | June 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Adenocarcinoma Stomach Neoplasms Esophageal Neoplasms Esophageal Squamous Cell Carcinoma Carcinoma, Squamous Cell Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Squamous Cell Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases |
Stomach Diseases Head and Neck Neoplasms Esophageal Diseases Fluorouracil Oxaliplatin Erlotinib Hydrochloride Fluorodeoxyglucose F18 Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Protein Kinase Inhibitors |