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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by WiSP Wissenschaftlicher Service Pharma GmbH
Sponsor:
Collaborator:
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
Information provided by (Responsible Party):
WiSP Wissenschaftlicher Service Pharma GmbH
ClinicalTrials.gov Identifier:
NCT01257360
First received: December 1, 2010
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Drug: Panitumumab
Radiation: Radiation of the pelvis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: NEO-RIT - Panitumumab in Combination With Radiotherapy in Patients With Locally Advanced RAS Wildtype Rectal Cancer (Clinical Stages II and III)

Resource links provided by NLM:


Further study details as provided by WiSP Wissenschaftlicher Service Pharma GmbH:

Primary Outcome Measures:
  • Rate of pathological complete remissions [ Time Frame: 15 weeks (average) after start of treatment (at surgery) ] [ Designated as safety issue: No ]
    The rate of pathological complete remissions is determined after tumor resection following neoadjuvant treatment.


Secondary Outcome Measures:
  • Toxicity according to NCI CTCAE [ Designated as safety issue: Yes ]
  • Frequency of surgical morbidity and complications [ Time Frame: Within four weeks after surgery ] [ Designated as safety issue: Yes ]
  • pTNM findings in relation to initial cTNM staging [ Time Frame: At surgery ] [ Designated as safety issue: No ]
  • Regression grading according to Dworak [ Time Frame: At surgery ] [ Designated as safety issue: No ]
  • Clinical response rates (CR/PR/SD/PD) after neoadjuvant treatment [ Time Frame: Before surgery ] [ Designated as safety issue: No ]
  • Correlative biomarker analyses [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: December 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    Other Name: Vectibix
    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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01257360

Contacts
Contact: Heiko Suelberg +49-2173-853130 info(@)wisp.de

Locations
Germany
Klinikum Esslingen Klinik für Onkologie, Gastroenterologie und Allgemeine Innere Medizin Recruiting
Esslingen, Germany, 73780
Principal Investigator: Michael Geissler, MD         
Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt am Main Recruiting
Frankfurt/Main, Germany, 60590
Principal Investigator: Claus Rödel, MD         
SLK-Kliniken Heilbronn GmbH Medizinische Klinik III Recruiting
Heilbronn, Germany, 74078
Principal Investigator: Uwe Martens, MD         
Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim Recruiting
Mannheim, Germany, 68167
Principal Investigator: Ralf Hofheinz, MD         
Prosper Hospital Medizinische Klinik I Recruiting
Recklinghausen, Germany, 45659
Principal Investigator: Michael Klein, MD         
Sponsors and Collaborators
WiSP Wissenschaftlicher Service Pharma GmbH
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
Investigators
Principal Investigator: Ralf Hofheinz, Prof. Dr. med. Tagestherapiezentrum am ITM & III. Medizinische Klinik, Universitätsmedizin Mannheim
  More Information

No publications provided

Responsible Party: WiSP Wissenschaftlicher Service Pharma GmbH
ClinicalTrials.gov Identifier: NCT01257360     History of Changes
Other Study ID Numbers: WISP_AG52, 2009-016782-28, GMIHO 009/2009
Study First Received: December 1, 2010
Last Updated: May 28, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by WiSP Wissenschaftlicher Service Pharma GmbH:
RAS-Wildtype
Radiotherapy
Neoadjuvant treatment

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on July 29, 2014