Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer (NEOREC-1)

This study has suspended participant recruitment.
(poor recruitment)
Sponsor:
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier:
NCT01443377
First received: August 23, 2011
Last updated: November 26, 2012
Last verified: April 2012
  Purpose

This study aims to investigate the combination of panitumumab and a 5-FU-based RCTX in patients with locally advanced KRAS wild-type rectal cancer.


Condition Intervention Phase
Rectal Cancer
Biological: Panitumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer

Resource links provided by NLM:


Further study details as provided by National Center for Tumor Diseases, Heidelberg:

Primary Outcome Measures:
  • Histopathological complete response rate (pCR) [ Time Frame: at week 14 after tumor resection ] [ Designated as safety issue: No ]
    pCR determined by means of the resection specimens


Secondary Outcome Measures:
  • Objective tumor response rate assessed by MRI of the pelvis (incl. RECIST) [ Time Frame: at day 14 and week 12 ] [ Designated as safety issue: No ]
  • Metabolic tumor response rate assessed by means of changes in the standardized uptake values (SUV) using FDG-PET-CT (incl. RECIST) [ Time Frame: day 14 and at week 14 before surgery ] [ Designated as safety issue: No ]
  • Pathological tumor regression grades will be classified according to Becker [ Time Frame: at week 14 after surgery ] [ Designated as safety issue: No ]
  • Quality of Life (QoL) will be assessed using the EORTC QLQ-C30 in combination with the colorectal cancer-specific quality of life questionaire module (QLQ-CR29) [ Time Frame: between day 0 and week 18 end of study ] [ Designated as safety issue: No ]
  • distant metastases-free survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]
    distant metastases-free survival after EOS

  • relapse-free survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]
    relapse-free survival after end of study

  • overall survival [ Time Frame: during follow up every 6 months until death or until 2 years after LPO ] [ Designated as safety issue: No ]
    overall survival after EOS


Estimated Enrollment: 48
Study Start Date: July 2011
Estimated Study Completion Date: September 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Panitumumab
    Intravenous (IV), Panitumumab 6 mg/kg BW q2w d1-d57 (5 times total); begin on day 1 (run-in-phase) and subsequent application on days 15, 29 43 and 57.
    Other Name: Vectibix®
Detailed Description:

Significant progress in the management of locally advanced rectal cancer has been achieved during the last decade. This includes surgical techniques as the widespread implementation of total mesorectal excision as well as preoperative radiochemotherapy (RCTX). The results of the recent randomized trials led to a current standard in which most (radio-) oncologists now use continuous-infusion 5-FU concomitantly with preoperative radiotherapy. It has been demonstrated that this provides improved tumor downstaging and local control; however, no significant differences have yet been achieved in the 5-year disease-free and overall survival rates.

Thus, the challenge is to integrate more effective systemic therapy into the combined-modality programs. The combination of RCTX with novel chemotherapeutic agents like oxaliplatin and irinotecan in phase I/II trials suggested higher rates of histopathological complete remission (pCR) compared with 5-FU RCTX alone. However, due to the lack of results from randomized trials, to date no improvement of the long-term outcomes could be demonstrated, moreover, for some studies the increased pCR rate was associated with an increase in toxicity.

Another strategy to improve outcome is to incorporate newer, biologically active, targeted therapies into established RCTX regimens. Because of its key role in signalling proliferation, inhibition of apoptosis and angiogenesis the epidermal growth factor receptor (EGFR) is a promising target of antitumor treatment. To date a few clinical phase I/II studies of preoperative RCTX have been initiated to evaluate EGFR inhibitors as radiosensitizer in rectal cancer. These trials demonstrated that a combination of cetuximab and RCTX could be safely applied without dose compromises of the respective treatment components. However, the pCR rates could not be improved in these studies.

Given the strong preclinical rationale to combine EGFR inhibition with RCTX in rectal cancer patients, this study aims to investigate the combination of panitumumab and a 5-FU-based RCTX in patients with locally advanced KRAS wild-type rectal cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed, potentially resectable rectal adenocarcinoma staged as uT3/4 N0/1 by endosonography or cT3/4 by MRI of the pelvis with or without local lymph node metastases.
  • Wild-type KRAS.
  • ECOG-performance status 0 or 1.
  • Age ≥ 18 years.
  • Laboratory requirements:

    • Haematology: Leucocyte count > 3,000/mm³, neutrophil count ≥1.5x109/L, hemoglobin ≥ 8 g/dL, platelet count ≥100x109/L.
    • Hepatic Function: Total bilirubin ≤ 1.5 time the upper normal limit (UNL), ASAT ≤ 2.5xUNL in absence of liver metastases or ≤ 5xUNL in presence of liver metastases, ALAT ≤ 2.5xUNL in absence of liver metastases or ≤ 5xUNL in presence of liver metastases
    • Renal Function: Creatinine clearance ≥50 mL/min or serum creatinine ≤1.5xUNL
    • Metabolic Function: Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal.
  • Negative ß-HCG-serum pregnancy test (females of child bearing potential).
  • Willing to use double-barrier contraception during study and for 6 months after the end of treatment.
  • Ability of patient to understand character and individual consequences of clinical trial
  • Written informed consent (must be available before enrollment in the trial)

Exclusion Criteria:

  • Prior EGFR targeting or prior chemo- or radiotherapy or tumor surgery.
  • Evidence of any distant metastases.
  • Manifest or previous secondary malignancies within the last 5 years.
  • Uncontrolled infection.
  • Clinically significant cardiovascular disease NYHA classification III or IV (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment/randomization.
  • History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on screening chest CT scan.
  • Diabetes mellitus
  • Subject pregnant or breast feeding, or planning to become pregnant within 6 month 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.
  • Active serious illness which renders the patient unsuitable for study entrance, multiple blood sampling or the above mentioned biopsies.
  • History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
  • Participation in other clinical trials or observation period of competing trials, respectively.
  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: NCT01443377

Locations
Germany
National Center for Tumor Disease (NCT)
Heidelberg, BW, Germany, 69120
Krankenhaus Nord West, Radioonkologische Klinik
Frankfurt, Hessen, Germany, 60488
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
Investigators
Principal Investigator: Dirk Jaeger, Prof. Dr National Center of Tumor Disease, Heidelberg
  More Information

No publications provided

Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT01443377     History of Changes
Other Study ID Numbers: NCT-0001021
Study First Received: August 23, 2011
Last Updated: November 26, 2012
Health Authority: Germany: Paul-Ehrlich-Institut
Germany: Federal Office for Radiation Protection

Keywords provided by National Center for Tumor Diseases, Heidelberg:
Neorec
rectal cancer
KRAS
Panitumumab
neoadjuvant
Radiochemotherapy
antibody
locally advanced KRAS wild type rectal cancer

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014