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

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

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.

Study Overview

• Status: Unknown
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Panitumumab; Radiation: Radiation of the pelvis

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Esslingen, Germany, 73780
    • Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin
  • Frankfurt/Main, Germany, 60590
    • Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main
  • Heilbronn, Germany, 74078
    • SLK-Kliniken Heilbronn GmbH Medizinische Klinik III
  • Mannheim, Germany, 68167
    • Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim
  • Recklinghausen, Germany, 45659
    • Prosper Hospital Medizinische Klinik I

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:

• 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

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Correlative biomarker analyses

Collaborators and Investigators

• Sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
• Collaborators: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
• Investigators: Principal Investigator: Ralf Hofheinz, Prof. Dr. med., Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): January 1, 2016
• Study Completion (Anticipated): July 1, 2016

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 8, 2010
• First Posted (Estimate): December 9, 2010

Study Record Updates

• Last Update Posted (Estimate): January 13, 2016
• Last Update Submitted That Met QC Criteria: January 12, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Radiotherapy; Neoadjuvant treatment; RAS-Wildtype
• 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: WISP_AG52; 2009-016782-28 (EudraCT Number); GMIHO 009/2009 (Other Identifier: GMIHO mbH)