Preoperative Panitumumab and Radiotherapy in Rectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate the activity of panitumumab in combination with standard preoperative radiotherapy in locally advanced rectal cancer, followed by complete surgery and adjuvant chemotherapy. The main hypothesis of the study is that the association of EGFR-targeting agent and radiation therapy could be as effective or even improve the rate of pathological complete tumoral response with fewer toxicities in comparison to the standard of care using chemoradiation therapy.

Detailed Description
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Anti-EGFR monoclonal antibodies have radiosensitizing properties. In particular, cetuximab in combination with curative-intent radiotherapy has been reported to increase median overall survival over radiation therapy alone in locally advanced head and neck carcinoma. Similar benefit in rectal cancer is expected. However, preliminary studies revealed that the combination of chemoradiation and cetuximab did not seem to improve the pathological tumor response. However, in the past studies, the selection of patients' population was not optimal since KRAS mutational status was not considered during recruitments. Therefore, new trials to investigate EGFR-targeting therapies in combination with radiotherapy in wild-type KRAS patients are required. Adjuvant chemotherapy has also shown to decrease the risk of local relapse in patients who did not receive chemotherapy during radiotherapy. In our study, since there will be no chemotherapy given during the preoperative setting, the administration of adjuvant chemotherapy postoperatively is highly recommended.

Official Title
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Phase II Study of Preoperative Panitumumab and External Beam Radiotherapy in Patients With Locally Advanced Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: panitumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG Performance Status 0-1 Histologically proven adenocarcinoma of the rectum, T3-T4 and/or N+ M0 Wild-type KRAS No prior pelvic irradiation Normal bone marrow, hepatic, renal, cardiac functions No secondary malignancy No other active, uncontrolled disease Signed informed consent Exclusion Criteria: KRAS mutation Established or suspected metastasis Prior pelvic irradiation Previous exposure to EGFR-targeting therapies Patients under any other investigational agent(s) Concurrent systemic immune therapy, chemotherapy, hormone therapy Drug and/or alcohol abuse Grade 3 to 4 allergic reaction to any of the components of the treatment History or presence of interstitial lung disease Active, uncontrolled cardiovascular disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: panitumumab<br> | Drug: panitumumab<br>* intravenous infusion of panitumumab, 6 mg per kg body weight, once every 14 days for a total of 42 days<br>* Other names: Vectibix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) |  | 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, pathologic R0 resection, negative Circumferential Resection Margin, pathologic downstaging, tumor regression grade, quality of mesorectal excision, rate of sphincter-preservation, Disease-Free Survival, local control rate, translational research |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectum, colorectal, cancer, adenocarcinoma, anti-EGFR, monoclonal antibodies, neoadjuvant therapy, preoperative radiotherapy