Panitumumab in Combination With Radiotherapy in Patients With Locally Advanced RAS Wildtype Rectal Cancer (Clinical Stages II and III)

NCT ID: NCT01257360

Last Updated: 2016-01-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2016-07-31

Brief Summary

The objective of this trial is to obtain evidence that, in patients with RAS wildtype tumors, a chemotherapy-free combined modality treatment with panitumumab is clearly superior to radiotherapy alone and achieves a pCR rate comparable to that after radiochemotherapy including two-drug combinations while reducing the toxicity compared to these two-drug regimens.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Panitumumab

Panitumumab 6 mg/kg BW will be administered IV every 2 weeks (q2w) on day -14, 1, 15, 29 (and 43, in case radiotherapy is still ongoing due to delays) of the radiotherapy.

Intervention Type: DRUG

Radiation of the pelvis

Radiation is applied at single doses of 1.8 Gy at the ICRU 50 reference point, once daily, five times a week, adding up to 28 fractions over almost 6 weeks and a total reference dose of 50.4 Gy.

Intervention Type: RADIATION

Other Intervention Names

Vectibix

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed diagnosis of locally advanced rectal cancer (stage II or III) localised 0 - 12 cm ab ano as measured by rigid rectoscopy (i.e. lower and middle third of the rectum)
• Staging requirements: trans-rectal endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI)
• Sufficient representative sample material for RAS analysis
• Wild-type RAS (determined by an accredited local laboratory, if not available by pathology of Mannheim university)

• RAS wild-type tested in

• KRAS exon 2 (codons 12/13)
• KRAS exon 3 (codons 59/61)
• KRAS exon 4 (codons 117/146)
• NRAS exon 2 (codons 12/13)
• NRAS exon 3 (codons 59/61)
• NRAS exon 4 (codons 117/146)
• Informed consent of the patient
• Aged at least 18 years
• WHO Performance Status 0-2
• Life expectancy of al least 12 weeks
• Adequate haematological, hepatic, renal and metabolic function parameters:

• Leukocytes > 3000/mm³
• ANC ≥ 1500/mm³
• Platelets ≥ 100,000/mm³
• Hb > 9 g/dl
• Creatinine clearance ≥ 50 ml/min and serum creatinine ≤ 1.5 x upper limit of normal
• Bilirubin ≤ 1.5 x upper limit of normal
• GOT-GPT ≤ 2.5 x upper limit of normal
• AP ≤ 5 x upper limit of normal
• Magnesium ≥ lower limit of normal
• Calcium ≥ lower limit of normal

Exclusion Criteria

• Lower border of the tumor localised more than 12 cm ab ano as measured by rigid rectoscopy
• Distant metastases (to be excluded by CT scan of the thorax and abdomen)
• cT4 tumor (as determined by MRI and/or endorectal ultrasound)
• Risk of tumor involvement of the circumferential resection margin, according to the MRI assessment
• Sphincter sparing is the major reason for choosing the neoadjuvant treatment approach
• Prior antineoplastic therapy for rectal cancer
• Prior radiotherapy of the pelvic region
• Major surgery within the last 4 weeks prior to inclusion
• Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment
• Subject (male or female) is 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 (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly)
• Serious concurrent diseases
• On-treatment participation in a clinical study in the period 30 days prior to inclusion
• Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrolment
• History of interstitial lung disease, e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• History of HIV infection
• Prior or concurrent malignancy (≤ 5 years prior to enrolment in study) except non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1 if the patient is continuously disease-free
• Known allergic reactions on study medication

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH

OTHER

Sponsor Role: collaborator

WiSP Wissenschaftlicher Service Pharma GmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralf Hofheinz, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim

Locations

Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin

Esslingen am Neckar, , Germany

Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main

Frankfurt am Main, , Germany

SLK-Kliniken Heilbronn GmbH Medizinische Klinik III

Heilbronn, , Germany

Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim

Mannheim, , Germany

Prosper Hospital Medizinische Klinik I

Recklinghausen, , Germany

Countries

Germany

Other Identifiers

2009-016782-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GMIHO 009/2009

Identifier Type: OTHER

Identifier Source: secondary_id

WISP_AG52

Identifier Type: -

Identifier Source: org_study_id