E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
neoadjuvant treatment in chemo-naive patients with newly diagnosed operable rectal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038038 |
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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 |
To evaluate the feasibility of three neo-adjuvant cycles of single agent Pemetrexed at 500 mg/m2 q3w prior to surgery with or without radiotherapy in patients with resectable rectal cancer. |
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E.2.2 | Secondary objectives of the trial |
• Pathological response rate (pCR) • Proportion of patients with sphincter saving surgery • Proportion of patients with complete tumor resection rate (CTRR) • Evaluation of qualitative and quantitative toxicities • mTHF tissue levels, comparisons of before vs. after folic acid dosing and tumor vs. normal tissue. • Correlation between mTHF and plasma Hcy levels. • Correlation of folate gene polymorphisms and micro array signature profiles with clinical outcome and toxicity profiles
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Pathological or cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to curative surgery.
2. No prior therapy for rectal cancer
3. Performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status scale. (see Protocol Attachment S077.2).
4. Adequate organ function that includes the following indices: adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) 1.5 109/L, platelet count 100 109/L, and hemoglobin 9 g/dL. hepatic: bilirubin 1.5 times the upper limit of normal ( ULN), alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) 3.0 ULN). renal: calculated creatinine clearance (CrCl) 45 mL/min by using the standard Cockcroft and Gault formula (see Protocol Attachment S077.3). Creatinine clearance enrollment and dosing decisions may be made on the basis of either local lab values or central laboratory values (the central laboratory reports the calculated value directly). A patient may be enrolled on the basis of the local lab values
5. Patient compliance and geographic proximity that allow adequate follow-up.
6. For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after treatment; must have a negative serum or urine pregnancy test (within 7 days before enrolment) and must not be lactating. For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after treatment. 7. Estimated life expectancy of at least 12 weeks. 8. Patients must sign an informed consent document, including consent to collection of tissue and blood samples as specified by the protocol.
9. Patients must be at least 18 years of age.
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E.4 | Principal exclusion criteria |
10. Concurrent administration of any other anti-tumor therapy 11. Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry 12. Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient’s ability to complete the study 13. Have previously completed or withdrawn from this study or any other study investigating Pemetrexed 14. Are pregnant or breast feeding 15. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment 16. History of significant neurological or mental disorder, including seizures or dementia 17. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before, the day of and 2 days after administration of Pemetrexed. If a patient is taking an NSAID or salicylate with a long half-life (e.g., naproxen, piroxicam, diflunisal, nabumetone, refexocib, celecoxib) it should not be taken 5 days before, the day of and 2 days after administration of Pemetrexed. 18. Presence of clinically relevant (i.e., detectable by physical examination) third-space fluid collection (e.g., ascites, pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry 19. Inability or unwillingness to take folic acid, vitamin B12, or dexamethasone
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of feasibility will be explored by evaluating the proportion of patients who receive the planned total dose as defined above. The proportion of patients who receive the planned total dose will be reported, including a 95% confidence interval. The estimate of this proportion will be given by Feasibility rate = Number of patients who received the planned total dose/ Number of patients qualified for feasibility analysis
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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end of the trial= all 40 patients have performed the 30 day safety post study treatment visit. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |