E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced cervical cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008233 |
E.1.2 | Term | Cervical cancer stage I |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008234 |
E.1.2 | Term | Cervical cancer stage II |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008235 |
E.1.2 | Term | Cervical cancer stage III |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008236 |
E.1.2 | Term | Cervical cancer stage IV |
E.1.2 | System Organ Class | 100000004864 |
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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 |
In women with locally advanced cervical cancer, does the addition of weekly chemotherapy prior to chemoradiation alone improve overall survival compared with chemoradiation alone? |
|
E.2.2 | Secondary objectives of the trial |
- In women with locally advanced cervical cancer, does the addition of weekly chemotherapy prior to chemoradiation alone improve disease free survival compared with chemoradiation alone? - What is the toxicity associated with the additional weekly chemotherapy treatment? - What are the effects on quality of life compared with the standard chemoradiation treatment? - Does the addition of weekly chemotherapy affect the pattern of relapse in this disease? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically confirmed FIGO stage Ib2- IVa squamous, adeno or adenosquamous carcinoma of the cervix (except FIGO IIIA) - Deemed suitable and fit for radical chemoradition - Medically fit to receive carboplatin and paclitaxel - ECOG performance status 0 – 1 - No evidence of active TB - Aged 18 and over - Adequate renal function, defined as a GFR >/= 60 ml/min calculated using the Wright equation ( or >/= 50 ml/min for radioisotope GFR assessment) - Adequate liver function, as defined by ALT or AST < 2.5 ULN and bilirubin < 1.25 ULN - Adequate bone marrow function as defined by ANC >/=1.5 x 109/L, platelets >/= 100 x 109/L - Using adequate contraception precautions if relevant - A documented negative HIV test (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries) - Capable of providing written or witnessed informed consent
Patients with positive nodes (either histologically/PET positive >/= 15 mm on CT/MR) at or below the level of the aortic bifurcation may be included in the study provided none of the exclusion criteria apply |
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E.4 | Principal exclusion criteria |
- Previous pelvic malignancy (regardless of interval since diagnosis) - Previous malignancy not affecting the pelvis (except basal cell carcinoma of the skin) where disease free interval is less than 10 years - Positive lymph nodes (imaging or histological) above the aortic bifurcation* - Hydronephrosis which has not undergone ureteric stenting or nephrostomy except where the affected kidney is non-functioning - Evidence of distant metastasis i.e. any non-nodal metastasis beyond the pelvis - Previous pelvic radiotherapy - Prior diagnosis of Crohn’s disease or Ulcerative colitis - Documented positive HIV antibody test or HIV viral load (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries) - Active TB - Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel) - Pregnant or lactating
* i.e. PET any size, CT/MRI >/= 15mm |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is overall survival. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Overall survival will be measured from the date of randomisation until the date of death from any cause. |
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E.5.2 | Secondary end point(s) |
Progression free survival Adverse events Quality of life Patterns of relapse |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression free survival will be measured from the date of randomisation until the date of first progression or death, whichever occurs first.
Adverse events will be collected weekly during treatment, 4 weeks post treatment, 3 monthly for 2 years and 6 monthly for 3 years.
Quality of life will be collected during treatment and at follow-up visits as outlined above.
Patterns of relapse (local and/or systemic) will be assessed during follow-up from the date of randomisation until the date of first relapse. |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 30 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
India |
Italy |
Mexico |
United Kingdom |
|
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
|
For regulatory purposes, the end of the trial will be 30 days after the last patient has completed 3 years of follow-up at which point the 'Declaration of End of Trial' form wil be submitted to participating regulatory authorities and ethical committees as required. Patients will then enter the follow-up phase of the study. |
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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 | 7 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 31 |