E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
p53 mutated epithelial ovarian cancer (after first line standard therapy), non-small cell lung cancer, small cell lung cancer, cervical and endometrial cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014733 |
E.1.2 | Term | Endometrial cancer |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041067 |
E.1.2 | Term | Small cell lung cancer |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055094 |
E.1.2 | Term | Cervix cancer metastatic |
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 | 20.0 |
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 safety and preliminary anti-tumor activity of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer in a 21 day schedule.
Additional safety and preliminary anti-tumor activity cohort:
To determine the safety and preliminary anti-tumor activity (RECIST 1.1) of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer, NSCLC, SCLC, cervical, and endometrial cancer, in a 21 day schedule.
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E.2.2 | Secondary objectives of the trial |
- To determine the pharmacokinetics of AZD1775 in plasma and of carboplatin in plasma and ultrafiltrates.
- To determine pharmacodynamic changes induced by AZD1775 in combination with carboplatin in both surrogate tissues (skin).
-To determine the time to progression.
Secondary objectives safety and preliminary anti-tumor activity cohort:
- To determine the time to progression.
- To determine the pharmacodynamic changes induced by AZD1775 in combination with carboplatin in circulating tumor cells (CTC).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. p53 mutated (determined by IHC and later by sequencing) epithelial ovarian cancer
2. measurable disease on CT scan
3. patients previously received standard 1st line platinum therapy (combined with paclitaxel) for epithelial ovarian cancer, and showed recurrence on or within 3 months of this treatment
4. age > 18 years
5. WHO performance status lower or equal to 1
1. histological or cytological proof of advanced epithelial ovarian cancer, NSCLC, SCLC, cervical and endometrial cancer (with proven p53 mutation).
2. previously treated with (standard) (1st) line platinum-based therapy (combined with paclitaxel in case of ovarian cancer ), and showed recurrence on or within 6 months after the end of this treatment.
3. Patients are allowed to have received second line non-platinum containing therapy after recurrence on 1st line treatment. No more than 2 lines of pre-treatment with cytotoxic chemotherapy are allowed.
4. Eligible patients will have p53 mutation determined by sequencing of exons 2-10.
5. Able and willing to undergo a tumor biopsy (if p53 status is already known, tumor biopsy is still mandatory). |
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E.4 | Principal exclusion criteria |
1. symptomatic cerebral or leptomeningeal metastases
2. current participation or previous participation in a study with an investigational compound, or chemo- and/or radiotherapy within 28 days of receiving first dose of study medication
3. patient must not have prior radiation therapy to more than 30% of the bone marrow and must have recovered for at least 3 weeks from the hematologic toxicity of prior radiotherapy.
Additional exclusion criteria for safety and activity cohort:
1. More than 2 lines pre-treatment with cytotoxic chemotherapy are not allowed. Only the first line will be carboplatin or cisplatin containing.
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase II proof-of-concept trial:
- to determine the safety and preliminary anti-tumor activity of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer in 21 day schedule.
Additional safety and preliminary anti-tumor activity cohort:
-to determine the safety and preliminary anti-tumor activity (RECIST 1.1) of AZD-1775 in combination with carboplatin in p53 mutated epithelial ovarian cancer, NSCLC, SCLC, cervical and endometrial cancer in a 21 day schedule. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety will be assessed on a continuous basis;
Preliminary anti-tumor activity will be assessed by CT-scan every 2 cycles (once per 6 weeks) and tumor markers (if applicable) every cycle (every 3 weeks). |
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E.5.2 | Secondary end point(s) |
secondary objectives proof-of-concept trial:
- To determine the pharmacokinetics (PK) of AZD1775 in plasma and of carboplatin in plasma and ultrafiltrates.
- To determine pharmacodynamics (PD) changes induced by AZD1775 in combination with carboplatin in surrogate tissues (skin)
- To determine the time to progression.
Secondary objectives safety and preliminary anti-tumor activity cohort:
- To determine the time to progression.
- To determine the pharmacodynamic changes induced by AZD1775 in combination with carboplatin in circulating tumor cells (CTC).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-PK and PD: at day 1 of cycle 1
-Time to progression: every 2 cycles (6 weeks) |
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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 | Yes |
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) | 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
| 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 | 2 |
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 | 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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Currently, the end of the trial for this study is not fixed. Patients will continue treatment untill progression of disease or intolerable side-effects. After discontinuation, patients will continue in a long-term follow-up phase untill death or lost to follow-up. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |