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

NCT01257360 | Unknown Phase 2 DMC

• 3 other identifiers: WISP_AG522009-016782-28GMIHO 009/2009
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 5

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

Keywords

RAS-Wildtype; Radiotherapy; Neoadjuvant treatment

Outcome Measures

Primary Outcomes (1)

• Rate of pathological complete remissions

  The rate of pathological complete remissions is determined after tumor resection following neoadjuvant treatment.

  15 weeks (average) after start of treatment (at surgery)

Secondary Outcomes (6)

• Toxicity according to NCI CTCAE

• Frequency of surgical morbidity and complications

  Within four weeks after surgery

• pTNM findings in relation to initial cTNM staging

  At surgery

• Regression grading according to Dworak

  At surgery

• Clinical response rates (CR/PR/SD/PD) after neoadjuvant treatment

  Before surgery

Interventions

Panitumumab DRUG

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.

Also known as: Vectibix

Radiation of the pelvis RADIATION

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• WiSP Wissenschaftlicher Service Pharma GmbH: lead
• Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH: collaborator

Study Sites (5)

Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin

Esslingen am Neckar, 73780, Germany

Location

Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

SLK-Kliniken Heilbronn GmbH Medizinische Klinik III

Heilbronn, 74078, Germany

Location

Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Prosper Hospital Medizinische Klinik I

Recklinghausen, 45659, Germany

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Panitumumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ralf Hofheinz, Prof. Dr. med.

  Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 9, 2010
• Study Start: December 1, 2010
• Primary Completion: January 1, 2016
• Study Completion: July 1, 2016
• Last Updated: January 13, 2016

Record last verified: 2016-01

Locations

DE (5)