Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas

A Pilot Study With Cetuximab and Radiation Therapy for Patients With Surgically Resectable Esophageal and GE Junction Carcinomas: Hoosier Oncology Group Study (GI05-92)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00319735

Enrollment

Registered

2006-04-27

Start date

2006-04-30

Completion date

2009-01-31

Last updated

2016-04-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Esophageal Cancer

Brief summary

The interaction of epidermal growth factor receptor (EGFR) inhibitory agents such as cetuximab combined with radiation shows promising results. EGFR inhibitory agents also enhance radiation-induced apoptosis and inhibit radiation induced damage repair. These interactions may represent the principle effects that contribute to the synergy between EGFR and radiation. This trial will investigate the feasibility and activity of this combination in patients with surgically resectable disease.

Detailed description

OUTLINE: This is a multi-center study. * Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose) * Cetuximab 250 mg/m2 IV over 60 minutes, day -7. * Cetuximab 250 mg/m2 IV over 60 minutes, days 1, 8, 15, 22, 29 and 36. * External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks. * Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy. * For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of cetuximab, and at the time of surgery for pathology submission.

Interventions

PROCEDURERadiation Therapy

External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks

PROCEDURESurgery

Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy

PROCEDURETissue Sample

For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction. * Clinical stage IIA, IIB or III without metastatic disease * Patients must have documented EGFR status or have tumor tissue available for assessment of EGFR status by IHC * Patients must be surgical candidates as determined by surgical consult. * Patients must agree to surgery. * ECOG performance status 0 or 2 * Absolute neutrophil count (ANC) \> 1,000 mm3 * Platelet count \> 75,000 mm3· Hemoglobin \> 10g/dL * Bilirubin \< 2.5 X upper limit of normal * AST (SGOT) or ALT (SGPT) \< 5.0 ´ upper limit of normal * Creatinine \< 2.0 X upper limit of normal

Exclusion criteria

* No history of or current brain metastasis. * No significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction. * No history of interstitial pneumonitis or pulmonary fibrosis, or suspicion of interstitial pneumonitis or pulmonary fibrosis on imaging. * No concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s). * No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction * No prior therapy that specifically and directly targets the EGFR pathway (such as kinase inhibitors and antibodies directed against the HER family receptors). * No prior severe infusion reaction to a monoclonal antibody. * No major surgery within 28 days prior to being registered for protocol therapy. * No clinically significant infections as judged by the treating investigator. * No acute hepatitis or known HIV. * No other active malignancies. * Negative pregnancy test. * No female patients currently breastfeeding.

Design outcomes

Primary

Measure	Time frame	Description
Complete Pathologic Response (pCR)	36 months	To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas. Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.

Secondary

Measure	Time frame	Description
Time to Relief of Dysphagia	36 months	To evaluate time to relief of dysphagia in patients with esophageal and GE junction carcinomas receiving preoperative radiation and cetuximab
Evaluate Toxicity	36 months	To evaluate the overall toxicities of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
Perform Exploratory Molecular Correlates.	36 months	To perform exploratory molecular correlates to determine the mechanisms of response and resistance to cetuximab and radiation therapy.
Complete and Partial Response Rate for Patients by Disease Stage: IIA	36 months	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
Complete Pathological Response Rate for Patients Who Underwent Esophagectomy.	Up to 36 months	To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas that underwent esophagectomy. Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.
Complete and Partial Response Rate for Patients by Disease Stage: III	36 months	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
Complete and Partial Response Rate for Patients by Histology: Adenocarcinoma	36 months	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
Complete and Partial Response Rate for Patients by Histology: Squamous Cell	36 months	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas
Complete and Partial Response Rate for Patients by Disease Stage: IIB	36 months	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas

Countries

United States

Participant flow

Participants by arm

Arm	Count
Single Arm Assignment Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose) Cetuximab 250 mg/m2 IV over 60 minutes Day -7 Cetuximab 250 mg/m2 IV over 60 minutes Days 1, 8, 15, 22, 29 and 36 Radiation Therapy: External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks Surgery: Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy Tissue Sample: For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission	41
Total	41

Arm

Count

Single Arm Assignment

Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose) Cetuximab 250 mg/m2 IV over 60 minutes Day -7 Cetuximab 250 mg/m2 IV over 60 minutes Days 1, 8, 15, 22, 29 and 36 Radiation Therapy: External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks Surgery: Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy Tissue Sample: For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	2

Baseline characteristics

Characteristic	Single Arm Assignment
Age, Customized Median	64 years
Disease Stage IIA	10 participants
Disease Stage IIB	7 participants
Disease Stage III	22 participants
Disease Stage IVA	2 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	26 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	13 participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	2 participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants
Histology Adenocarcinoma	32 participants
Histology Squamous cell carcinoma	9 participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	4 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	36 Participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	38 Participants
Tumor Site Esophagus	26 participants
Tumor Site Gastroesophageal Junction	15 participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	39 / 41
serious Total, serious adverse events	16 / 41

Outcome results

Primary

Complete Pathologic Response (pCR)

To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas. Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.

Time frame: 36 months

Arm	Measure	Value (NUMBER)
Single Arm Assignment	Complete Pathologic Response (pCR)	36.6 percentage of participants

Secondary