Clinical trial NCT01257360: Panitumumab in Combination With Radiotherapy in Patients With Locally Advanced RAS Wildtype Rectal Cancer (Clinical Stages II and III)
Official title: NEO-RIT - Panitumumab in Combination With Radiotherapy in Patients With Locally Advanced RAS Wildtype Rectal Cancer (Clinical Stages II and III)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: RAS-Wildtype
Radiotherapy
Neoadjuvant treatment
Lead sponsor: WiSP Wissenschaftlicher Service Pharma GmbH
Sponsor class: OTHER
Collaborators: name: Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
First posted: 2010-12-09
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Rate of pathological complete remissions
timeFrame: 15 weeks (average) after start of treatment (at surgery)
Secondary outcomes:
measure: Toxicity according to NCI CTCAE
measure: Frequency of surgical morbidity and complications
timeFrame: Within four weeks after surgery
measure: pTNM findings in relation to initial cTNM staging
timeFrame: At surgery
measure: Regression grading according to Dworak
timeFrame: At surgery
measure: Clinical response rates (CR/PR/SD/PD) after neoadjuvant treatment
timeFrame: Before surgery
measure: Correlative biomarker analyses
Other outcomes:
Locations:
city: Esslingen
country: Germany
facility: Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin
city: Frankfurt/Main
country: Germany
facility: Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH Medizinische Klinik III
city: Mannheim
country: Germany
facility: Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim
city: Recklinghausen
country: Germany
facility: Prosper Hospital Medizinische Klinik I
Study officials:
affiliation: Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim
name: Ralf Hofheinz, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: