E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with BRCA1- or BRCA2-associated advanced breast- and ovarian cancer which are refractory to standard therapy and for which no suitable, effective/curative therapy exists. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced breast- and ovarian cancer which are refractory to standard therapy and for which no suitable, effective/curative therapy exists |
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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 | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 |
Tumor response (i.e. non-progressive disease) after 2 and 4 cycles of chemotherapy / at week 12 and 24 (assessed using the principles of RECIST 1.1, based on confirmed response) |
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E.2.2 | Secondary objectives of the trial |
Tumor response (OR) after 6 cycles of chemotherapy /at week 36, PFS, OS, DOR and DCR, health-related quality of life (EORTC QLQ C30 and EQ-5D), ECOG Performance Status |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female BRCA1 and BRCA2 mutation carriers
• Histological confirmed breast or ovarian cancer
• Refractory to standard therapies and for which no suitable effective standard therapy exists
• Age ≥18 years
• ECOG 0-2 with adequate cardiac, bone marrow (platelet count >/= 100x109/l), hepatic (total bilirubin </=1.5 x institutional upper limit of normal (ULN); ASAT/ALT </= 2.5 x institutional ULN unless liver metastases are present in which case it must be </= 5 x ULN) and renal function
• Patients must have a life expectancy >/= 3 months
• Postmenopausal or use of adequate contraceptive during chemotherapy and six months thereafter
• Fully informed consent prior to study-specific procedures
• Patient is willing and able to comply with the protocol for the duration of the study including treatment and scheduled visits and examinations
• At least one lesion (measurable and/or non-measurable) at baseline that can be accurately assessed by CT/MRI and is suitable for repeated assessment at follow-up visits
• All baseline radiological tumour assessments must be performed no earlier than 21 days before start of the study treatment.
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E.4 | Principal exclusion criteria |
• Pregnant or nursing patients
• Prior chemotherapy with nitroso-urea substances for any malignancy
• Concurrent treatment with other experimental drugs or any other anti-cancer therapy
• Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons) within 2 weeks from the last dose prior to study treatment.
• Nicotine abuse
• Limited pulmonary function
• Pre-existing pulmonary diseases (e.g. chronic obstructive pulmonary disease/COPD, fibrosis)
• Prior radiation including areas of the lung (except radiation of the breast after breast conserving surgery).
• Pre-existing radiographical alterations of the lung
• Any psychological, sociological or geographical condition potentially impeding compliance with study protocol or follow-up
• Known or suspected allergy to the BCNU
• Failure to use highly-effective contraceptive
• Persistent toxicities (>CTCAE grade 2) caused by previous therapies
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumor response (i.e. non-progressive disease) after 2 and 4 cycles of chemotherapy / at week 12 and 24 (assessed using the principles of RECIST 1.1, based on confirmed response) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 12 and 24 weeks (2 and 4 cycles) of chemotherapy |
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E.5.2 | Secondary end point(s) |
Secondary objective is the efficacy of the treatment measured by tumor response after 6 cycles of chemotherapy /at week 36 (assessed by OR, PFS, OS, DOR and DCR, health-related quality of life (EORTC QLQ C30 and EQ-5D), ECOG Performance Status). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 36 weeks (6 cycles) of chemotherapy |
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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 | 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 | Yes |
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
| 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |