E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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, but without evidence of distant metastases. |
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E.1.1.1 | Medical condition in easily understood language |
Enddarmkrebs, der noch in einem recht frühen Stadium entdeckt wurde und noch nicht in weitere Organe gestreut hat (lokal fortgeschrittenes Rektumkarzinom) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038052 |
E.1.2 | Term | Rectal carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the anti-tumor efficacy of Panitumumab with combined radiochemotherapy with respect to the pCR rate. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include metabolic, objective response, and further pathological efficacy parameter as well as safety parameter and quality of life. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Same Protocol - Description of the sub-study and its objectives:
Response to anti-EGFR-treatment
Tumor-infiltrating immune cells, tumor microenvironment and tumor-associated autoantibodies as prognostic tool in the treatment of colorectal cancer |
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E.3 | Principal inclusion criteria |
o 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. o Wild-type KRAS. o ECOG-performance status 0 or 1. o Age ≥ 18 years. o 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. o Negative ß-HCG-serum pregnancy test (females of child bearing potential). o Willing to use double-barrier contraception during study and for 6 months after the end of treatment. o Ability of patient to understand character and individual consequences of clinical trial o Written informed consent (must be available before enrolment in the trial)
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E.4 | Principal exclusion criteria |
o Prior EGFR targeting or prior chemo- or radiotherapy or tumor surgery. o Evidence of any distant metastases. o Manifest or previous secondary malignancies within the last 5 years. o Uncontrolled infection. o 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 enrolment/randomization. o History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on screening chest CT scan. o Diabetes mellitus o Subject pregnant or breast feeding, or planning to become pregnant within 6 month after the end of treatment. o 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. o Active serious illness which renders the patient unsuitable for study entrance, multiple blood sampling or the above mentioned biopsies. o 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. o Participation in other clinical trials or observation period of competing trials, respectively.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the histopathological complete response rate (pCR) determined by means of the resection specimens. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of study (week 14 +/-7) |
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E.5.2 | Secondary end point(s) |
Secondary endpoints will be objective tumor response rates of the pelvis and metabolic tumor response rates assessed by means of changes in the standardized uptake values (SUV) using FDG-PET-CT. Further secondary endpoints are the rate of R0 and sphincter preserved resections. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At day 14 by MRT Before surgery (week 12) tumor response rates will be reassessed by MRI of the pelvis and FDG-PET-CT |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |