Preoperative Panitumumab and Radiotherapy in Rectal Cancer (PrePaRad)

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

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.

Study Overview

• Status: Terminated
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: panitumumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institute Jules Bordet
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint Luc - Université Catholique de Louvain
  • Charleroi, Belgium, 6000
    • Centre Hospitalier Notre Dame et Reine Fabiola
  • La Louvière, Belgium, 7100
    • Centre Hospitalier de Jolimont-Lobbes
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg
  • Namur, Belgium, 5000
    • Clinique et Maternité Saint Elizabeth
  • Ottignies, Belgium, 1340
    • Clinique Saint Pierre
  • Yvoir, Belgium, 5530
    • Clinique Universitaire de Mont Godinne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: panitumumab	Drug: panitumumab; intravenous infusion of panitumumab, 6 mg per kg body weight, once every 14 days for a total of 42 days; Other Names: Vectibix

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Jean-Pascal H Machiels, MD, PhD, Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 7, 2009
• First Submitted That Met QC Criteria: September 8, 2009
• First Posted (Estimate): September 9, 2009

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 19, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: cancer; colorectal; neoadjuvant therapy; adenocarcinoma; monoclonal antibodies; rectum; anti-EGFR; preoperative radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Panitumumab
• Other Study ID Numbers: UCL-ONCO 09-001; Academic study