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

Rectal Cancer Clinical Trial

— NEO-RIT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01257360
• Other study ID #: WISP_AG52
• Secondary ID: 2009-016782-28GM
• Status: Active, not recruiting
• Phase: Phase 2
• First received: December 1, 2010
• Last updated: January 12, 2016
• Start date: December 2010
• Est. completion date: July 2016

Study information

• Verified date: January 2016
• Source: WiSP Wissenschaftlicher Service Pharma GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 59
• Est. completion date: July 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• Panitumumab
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.

Radiation:
• Radiation of the pelvis
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.

Locations

Country	Name	City	State
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	Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim	Mannheim
Germany	Prosper Hospital Medizinische Klinik I	Recklinghausen

Sponsors (2)

Lead Sponsor	Collaborator
WiSP Wissenschaftlicher Service Pharma GmbH	Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Toxicity according to NCI CTCAE			Yes
Secondary	Frequency of surgical morbidity and complications		Within four weeks after surgery	Yes
Secondary	pTNM findings in relation to initial cTNM staging		At surgery	No
Secondary	Regression grading according to Dworak		At surgery	No
Secondary	Clinical response rates (CR/PR/SD/PD) after neoadjuvant treatment		Before surgery	No
Secondary	Correlative biomarker analyses			No