E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced RAS wildtype rectal cancer (clinical stage II and III) |
lokal fortgeschrittenes RAS Wildtyp Rektumkarzinom (klinische Stadien II und III) |
|
E.1.1.1 | Medical condition in easily understood language |
Locally advanced RAS wildtype rectal cancer (clinical stage II and III) |
lokal fortgeschrittenes RAS Wildtyp Rektumkarzinom (klinische Stadien II und III) |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038050 |
E.1.2 | Term | Rectal cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038049 |
E.1.2 | Term | Rectal cancer stage II |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 |
The primary objective of the study is to estimate the efficacy of panitumumab concurrent to radiotherapy in
patients with wild-type RAS. The rate of pathological complete remissions will be compared to expectations
derived from historical data. |
|
E.2.2 | Secondary objectives of the trial |
- Safety of the combination (Toxicity assessment according to NCI CTCAE V.3)
- Surgical morbidity and complications
- Pathological staging, tumor downstaging; assessed by pTNM findings in
relation to initial cTNM staging; regression grading according to Dworak
- Clinical response (rates of CR/PR/SD/PD after neoadjuvant treatment)
- Biomarker studies (KRAS, NRAS, BRAF, PI3K-Akt, PTEN, EGFR) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Locally advanced rectal cancer (stage II or III; EUS and MRI mandatory)
• RAS wildtype mandatory (to be determined at accredited local
laboratory or pathology of Mannheim Univ.)
• 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)
• PTEN expression result available (IHC - to be determined by pathology of
Mannheim Univ.)
• adequate hematologic, hepatic, renal and metabolic parameters
E. |
|
E.4 | Principal exclusion criteria |
• Distant metastases (excluded by CT scan)
• cT4 tumor (excluded by MRI and EUS)
• Risk of tumor involvement of the circumferential resection margin, according to the
MRI assessment
• Sphincter sparing as the major reason for choosing the neoadjuvant treatment
approach
• Prior antineoplastic therapy for rectal cancer |
|
E.5 End points |
E.5.1 | Primary end point(s) |
pCR rate, defined by the number of patients with a pCR finding divided by the number of patients recruited and
having received at least one application of antitumor therapy |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At surgical resection of the rectal tumor |
|
E.5.2 | Secondary end point(s) |
1. Safety of the combination (Toxicity assessment according to NCI CTCAE V.4)
2. Surgical morbidity and complications
3. Pathological staging, tumor downstaging; assessed by pTNM findings in relation to initial cTNM staging; regression grading according to Dworak
4. Clinical response (rates of CR/PR/SD/PD after neoadjuvant treatment)
5. Biomarker studies (KRAS, BRAF, PI3K-Akt, PTEN, EGFR) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During radio-"immunotherapy"
2. At surgery and 4 weeks after surgery
3. At surgical resection of the rectal tumor
4. At surgical resection of the rectal tumor
5. At inclusion in the study and at surgical resection of the rectal tumor |
|
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 | Yes |
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 | 5 |
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
|
Cf.section 5.11 of the protocol |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |