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

WiSP Wissenschaftlicher Service Pharma

Status and phase

Unknown

Phase 2

Conditions

Rectal Cancer

Treatments

Drug: Panitumumab

Radiation: Radiation of the pelvis

Study type

Interventional

Funder types

Other

Identifiers

NCT01257360

2009-016782-28 (EudraCT Number)

GMIHO 009/2009 (Other Identifier)

WISP_AG52

Details and patient eligibility

About

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.

Enrollment

59 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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