E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or metastatic breast or ovarian cancer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028985 |
E.1.2 | Term | Neoplasm breast |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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 |
To determine the anti-cancer activity of 6MP with low dose Methotrexate in patients with breast, ovarian, fallopian tube or primary serous peritoneal cancer and a known BRCA mutation.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to assess: - progression of the disease(progression free survival) - Overall survival (survival at 1-2 years) - safety and tolerability of 6MP with Methotrexate. - the biochemical response rates for ovarian, fallopian tube or primary serous peritoneal cancer based on changes in the serum levels of CA125, a cancer antigen. - Assessment of the TPMT genotype using a validated assay. - quality of life (QOL) of the patients enrolled. In addition, this study will look at the rates of recruitment to determine the feasibility of performing studies in small patient subgroups with BRCA mutated cancer.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients with proven BRCA1 or BRCA2 mutations and after appropriate exposure to standard treatment, as defined by:
Breast Cancer a) Patients with initially histologically or cytologically proven locally advanced or metastatic breast cancer who may have received up to 3 previous lines of chemotherapy in the locally advanced or metastatic breast cancer setting. b) Patients must have previously had a taxane and an anthracycline in either the adjuvant or metastatic setting, provided that these were not contraindicated(by patient toxicities or patient refusal). c) Patients with hormone responsive disease should have had at least 1 line of hormone therapy for metastatic disease unless contraindicated (by expected toxicities or patient refusal). d) Prior treatment with a PARP inhibitor is permissible.
OR
Ovarian/ Fallopian tube/ Primary Serous Peritoneal Cancer a) Patients with initially histologically or cytologically proven ovarian, fallopian tube or primary serous peritoneal cancer. b) Patients must have disease that is platinum resistant or in whom further platinum based therapy is inappropriate. c) Prior treatment with a PARP inhibitor is permissible.
2. Patients must have measurable disease as defined by RECIST v1.1 criteria; 3. Age ≥18 years 4. ECOG performance score of 0-2 5. Life expectancy of >12 weeks 6. Adequate haematological and biochemical function. 7. Written informed consent 8. No prior anti-cancer treatment in previous 4 weeks, other than palliative RT. 9. Haematological and biochemical indices within the ranges given at screening and on cycle 1 day 1. 10. Ascites and pleural effusions must be drained prior to therapy |
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E.4 | Principal exclusion criteria |
1. Patients with any of the following contra-indications to thiopurines (6MP/ 6TG) or methotrexate: • family history of severe liver failure; • porphyria; • diffuse infiltrative pulmonary or pericardial disease; • known hypersensitivity to either trial agent. 2. Patients found to have a Low/Low genotype on TPMT testing will be excluded. 3. Pregnant or breast-feeding women 4. Any other active malignancy requiring treatment/ or whose prognosis will prevent readout from trial endpoints. 5. Patients known or tested to be serologically positive for Hepatitis B, Hepatitis C or HIV. 6. Patients with active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery and/or whole brain radiotherapy are eligible if the patient remains without evidence of disease progression in brain ≥ 3 months prior to registration date. They must also be off corticosteroid therapy for ≥ 3 weeks prior to registration date. 7. Patients who have received anticancer agent(s) or an investigational agent within 28 days prior to study drug administration. 8. Subjects who have not recovered to within one grade level (not to exceed grade 2) of their baseline following a significant adverse event or toxicity attributed to previous anticancer treatment are excluded.
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the objective response rate at 8 weeks to 6MP/methotrexate in this patient population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Disease response at 8 weeks using RECIST v1.1. |
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E.5.2 | Secondary end point(s) |
To evaluate overall survival after treatment with 6MP/methotrexate. To evaluate progression free survival (PFS) after treatment with 6MP/methotrexate. Safety of 6MP/methotrexate. To study the effect of patient pharmacogenomics on thiopurine metabolism. Assessment of feasibility as a multi-centre study. Assessment of quality of life. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival after treatment with 6MP/methotrexate, including at 1 and 2 years. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 15 |
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 | No |
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 trial is defined as last visit of last patient undergoing trial treatment. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |