Panitumumab, Combination Chemotherapy, & Radiation Therapy in Esophageal or Gastroesophageal Junction Cancer

NCT01307956 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 0221-09-FBNCI-2010-02056P30CA036727
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well giving panitumumab, combination chemotherapy, and radiation therapy together before surgery works in treating patients with advanced esophageal or gastroesophageal (GE) junction cancer. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells. Giving monoclonal antibody therapy together with chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Complete Pathological Response (pCR) Rate

  Based on the proportion who achieve pCR based on the first 4 courses of protocol treatment. Evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Means (with associated standard errors), medians (with ranges), percentages and 95% confidence intervals will be reported as appropriate.

  Up to 8 weeks

Secondary Outcomes (1)

• Number of Patients Who Can Undergo Resection

  4 weeks after completion of the radiation

Other Outcomes (2)

• Progression-free Survival

  Patients were followed from time of consent until the date of first documented progession or date of death from any cause, whichever came first, assessed up to 100 months.

• Overall Survival

  From the first date of therapy until the date the patient dies, assessed up to 100 months

Study Arms (1)

Treatment (panitumumab, chemotherapy, radiation)

EXPERIMENTAL

Patients receive panitumumab IV over 1 hour on day 1. Patients also receive oxaliplatin IV and leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1 (FOLFOX chemotherapy). Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Within 24 hours of the start of chemotherapy, patients undergo radiation therapy 5 days a week for 5.5 weeks. Patients then undergo surgery within 6-8 weeks after completion of radiation therapy. Patients with residual disease receive 4 additional courses of FOLFOX chemotherapy on days 1, 15, 29, and 42.

Drug: Fluorouracil; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Oxaliplatin; Biological: Panitumumab; Other: Pharmacological Study; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Interventions

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (panitumumab, chemotherapy, radiation)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (panitumumab, chemotherapy, radiation)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (panitumumab, chemotherapy, radiation)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (panitumumab, chemotherapy, radiation)

Panitumumab BIOLOGICAL

Given IV

Also known as: ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, MoAb ABX-EGF, Monoclonal Antibody ABX-EGF, Vectibix

Treatment (panitumumab, chemotherapy, radiation)

Pharmacological Study OTHER

Correlative studies

Treatment (panitumumab, chemotherapy, radiation)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (panitumumab, chemotherapy, radiation)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Treatment (panitumumab, chemotherapy, radiation)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have resectable adenocarcinoma of the esophagus or GE-junction and are medically fit to undergo surgery; patients must have no evidence of distant metastasis based on imaging studies
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) of at least 2000 per mcL
• Platelet count of at least 100,000 per mcL
• Serum creatinine less than or equal to 2.0 mg/dL
• Serum magnesium greater than or equal to 1.8 mg/dL
• Total bilirubin less than or equal to 2.0 mg per dL
• Measurable disease is not required for this study, since the primary endpoint is complete pathologic response
• The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

You may not qualify if:

• Prior therapy: patients with prior history of mediastinal radiation exposure will be ineligible; patients may not have received prior chemotherapy, or antibody therapy for esophageal or GE-junction adenocarcinoma
• History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
• Patients with a prior history of marked intolerance to 5-fluoropyrimidines (5-FU, floxuridine, capecitabine, 5-fluorocytosine \[flucytosine\]), since such patients may have deficiency of dihydropyrimidine dehydrogenase, which places them at risk for severe and life-threatening toxicity with 5-FU
• Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, ongoing immunosuppressive therapy (except for replacement steroids), active human immunodeficiency virus (HIV) infection, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
• Clinically significant cardiac disease (including symptomatic congestive heart failure, myocardial infarction, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia) within 1 year of study enrollment
• Pregnant and nursing women, or women planning to become pregnant within 6 months after the end of treatment, are excluded from this study; a negative pregnancy test will be required of women of child-bearing age within 72 hours of study enrollment; subjects (male or female) who are not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment are excluded
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
• Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
• Patients receiving an investigational agent within 30 days before enrollment

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Interventions

Fluorouracil; dehydroftorafur; Leucovorin; Oxaliplatin; Panitumumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Jean L Grem
• Organization: University of Nebraska Medical Center

jgrem@unmc.edu

402-559-5166

Study Officials

• Jean L Grem, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 3, 2011
• Study Start: February 28, 2011
• Primary Completion: December 23, 2015
• Study Completion: December 23, 2015
• Last Updated: October 26, 2023
• Results First Posted: March 13, 2018

Record last verified: 2023-10

Locations

US (1)