- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01443377
Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer (NEOREC-1)
Study Overview
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
BW
-
Heidelberg, BW, Germany, 69120
- National Center for Tumor Disease (NCT)
-
-
Hessen
-
Frankfurt, Hessen, Germany, 60488
- Krankenhaus Nord West, Radioonkologische Klinik
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Histopathological complete response rate (pCR)
Time Frame: at week 14 after tumor resection
|
pCR determined by means of the resection specimens
|
at week 14 after tumor resection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective tumor response rate assessed by MRI of the pelvis (incl. RECIST)
Time Frame: at day 14 and week 12
|
at day 14 and week 12
|
|
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
|
day 14 and at week 14 before surgery
|
|
Pathological tumor regression grades will be classified according to Becker
Time Frame: at week 14 after surgery
|
at week 14 after surgery
|
|
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
|
between day 0 and week 18 end of study
|
|
distant metastases-free survival
Time Frame: during follow up every 6 months until death or until 2 years after LPO
|
distant metastases-free survival after EOS
|
during follow up every 6 months until death or until 2 years after LPO
|
relapse-free survival
Time Frame: during follow up every 6 months until death or until 2 years after LPO
|
relapse-free survival after end of study
|
during follow up every 6 months until death or until 2 years after LPO
|
overall survival
Time Frame: during follow up every 6 months until death or until 2 years after LPO
|
overall survival after EOS
|
during follow up every 6 months until death or until 2 years after LPO
|
Collaborators and Investigators
Investigators
- Principal Investigator: Dirk Jaeger, Prof. Dr, National Center of Tumor Disease, Heidelberg
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCT-0001021
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rectal Cancer
-
Ohio State University Comprehensive Cancer CenterNovartis Pharmaceuticals; National Comprehensive Cancer NetworkCompletedStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Recurrent Rectal CancerUnited States
-
M.D. Anderson Cancer CenterRecruitingEvaluation of Quality of Life and Utilities Following Surgical Treatment of Stage I-IV Rectal CancerStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Stage IV Rectal Cancer AJCC v8 | Stage IVA Rectal Cancer AJCC v8 | Stage IVB Rectal Cancer AJCC v8 | Stage IVC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage... and other conditionsUnited States
-
OHSU Knight Cancer InstituteNatera, Inc.RecruitingEstablishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal CancerStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8United States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8United States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)WithdrawnStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Rectal AdenocarcinomaUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science University; Taiho Pharmaceutical Co., Ltd.RecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8United States
-
Jonsson Comprehensive Cancer CenterNatera, Inc.; The Joseph Drown FoundationRecruitingStage III Rectal Cancer AJCC v8 | Stage IIIA Rectal Cancer AJCC v8 | Stage IIIB Rectal Cancer AJCC v8 | Stage IIIC Rectal Cancer AJCC v8 | Rectal Adenocarcinoma | Stage IIA Rectal Cancer AJCC v8 | Stage IIB Rectal Cancer AJCC v8 | Stage II Rectal Cancer AJCC v8 | Stage IIC Rectal Cancer AJCC v8 | Locally...United States
-
Case Comprehensive Cancer CenterCompletedStage IIA Rectal Cancer | Stage IIB Rectal Cancer | Stage IIC Rectal Cancer | Stage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Recurrent Colon Cancer | Recurrent Rectal Cancer | Stage IVA Colon Cancer | Stage IVA Rectal Cancer and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Rectal Adenocarcinoma | Rectal Adenocarcinoma | Stage III Rectal Cancer AJCC v7 | Stage IIIA Rectal Cancer AJCC v7 | Stage IIIB Rectal Cancer AJCC v7 | Stage IIIC Rectal Cancer AJCC v7 | Stage IV Rectal Cancer AJCC v7 | Stage IVA Rectal Cancer AJCC v7 | Stage IVB Rectal Cancer AJCC v7 | Locally...United States
-
City of Hope Medical CenterWithdrawnRecurrent Rectal Cancer | Stage I Rectal Cancer | Stage II Rectal Cancer | Stage III Rectal Cancer
Clinical Trials on Panitumumab
-
University of Alabama at BirminghamRecruiting
-
Spanish Cooperative Group for the Treatment of...AmgenCompleted
-
Radboud University Medical CenterTerminatedIrresectable Squamous Cell or Adenocarcinoma of the OesophagusNetherlands
-
TakedaCompleted
-
WiSP Wissenschaftlicher Service Pharma GmbHGesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbHTerminatedUrinary Bladder CancerGermany
-
Cliniques universitaires Saint-Luc- Université...Terminated
-
Gruppo Oncologico del Nord-OvestCompletedMetastatic Colo-rectal CancerItaly
-
University of UtahTerminatedKRAS and NRAS Wild-type Colorectal CancerUnited States
-
Hellenic Cooperative Oncology GroupCompleted
-
Matteo's FriendsRecruitingRecurrence Free SurvivalItaly