Clinical trial NCT00973193: Preoperative Panitumumab and Radiotherapy in Rectal Cancer
Official title: Phase II Study of Preoperative Panitumumab and External Beam Radiotherapy in Patients With Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: rectum
colorectal
cancer
adenocarcinoma
anti-EGFR
monoclonal antibodies
neoadjuvant therapy
preoperative radiotherapy
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2009-09-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathological Complete Response (pCR)
timeFrame: 11 weeks
Secondary outcomes:
measure: 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
timeFrame: 24 months
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Institute Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc - Université Catholique de Louvain
city: Charleroi
country: Belgium
facility: Centre Hospitalier Notre Dame et Reine Fabiola
city: La Louvière
country: Belgium
facility: Centre Hospitalier de Jolimont-Lobbes
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Namur
country: Belgium
facility: Clinique et Maternité Saint Elizabeth
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
city: Yvoir
country: Belgium
facility: Clinique Universitaire de Mont Godinne
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Jean-Pascal H Machiels, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: