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Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer

Phase 2
18 Years
Not Enrolling
Rectal Cancer

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Trial Information

Neoadjuvant Radiochemotherapy Combined With Panitumumab in Locally Advanced KRAS Wild-type Rectal Cancer

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.

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

- 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

- 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

- 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,

Type of Study:


Study Design:

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

Outcome Measure:

Histopathological complete response rate (pCR)

Outcome Description:

pCR determined by means of the resection specimens

Outcome Time Frame:

at week 14 after tumor resection

Safety Issue:


Principal Investigator

Dirk Jaeger, Prof. Dr

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Center of Tumor Disease, Heidelberg


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

July 2011

Completion Date:

September 2013

Related Keywords:

  • Rectal Cancer
  • Neorec
  • rectal cancer
  • KRAS
  • Panitumumab
  • neoadjuvant
  • Radiochemotherapy
  • antibody
  • locally advanced KRAS wild type rectal cancer
  • Rectal Neoplasms