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

Phase 2

• Conditions: Rectal Cancer

• Registration Number: NCT01257360
• Lead Sponsor: WiSP Wissenschaftlicher Service Pharma GmbH

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-01
• Study First Submitted QC: 2010-12-08
• Study First Posted: 2010-12-09
• Status Verified: 2016-01
• Primary Completion: 2016-01
• Last Update Submitted: 2016-01-12
• Last Update Posted: 2016-01-13
• Study Completion: 2016-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 59

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Rate of pathological complete remissions	15 weeks (average) after start of treatment (at surgery)	The rate of pathological complete remissions is determined after tumor resection following neoadjuvant treatment.

Secondary Outcome Measures

Name	Time	Method
Clinical response rates (CR/PR/SD/PD) after neoadjuvant treatment	Before surgery
Correlative biomarker analyses
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

Trial Locations

Locations (5)

Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim; 🇩🇪 Mannheim, Germany

Prosper Hospital Medizinische Klinik I; 🇩🇪 Recklinghausen, Germany

Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin; 🇩🇪 Esslingen, Germany

Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main; 🇩🇪 Frankfurt/Main, Germany

SLK-Kliniken Heilbronn GmbH Medizinische Klinik III; 🇩🇪 Heilbronn, Germany