E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057529 |
E.1.2 | Term | Ovarian 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033131 |
E.1.2 | Term | Ovarian carcinoma |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070905 |
E.1.2 | Term | Ovarian cancer stage I |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070906 |
E.1.2 | Term | Ovarian cancer stage II |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070907 |
E.1.2 | Term | Ovarian cancer stage III |
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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070908 |
E.1.2 | Term | Ovarian cancer stage IV |
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 | LLT |
E.1.2 | Classification code | 10007107 |
E.1.2 | Term | Cancer of ovary |
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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026310 |
E.1.2 | Term | Malignant neoplasm of ovary |
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 |
The primary objective of this study is to investigate the progression-free survival (PFS) according to RECIST 1.1 criteria on matched targeted therapy by signal transduction activation (STA)-analysis (PFS2) in comparison to the PFS recorded on the therapy administered prior to enrolment (PFS1) in recurrent ovarian cancer patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to investigate the: 1. Proportion of patients with an actionable active pathway for which targeted therapy is recommended. 2. Proportion of patients who receive matched targeted therapy. 3. Best overall response defined by RECIST 1.1 criteria. 4. One-year survival and overall survival. 5. Predictive value of STA-analysis results (and if available, immunohistochemical biomarker analysis / DNA sequencing results) on matched targeted therapy response. 6. Side effects 7. Health-related quality of life (HRQoL) 8. Cost-effectiveness |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age > 18 years. - Patients with recurrent ovarian cancer who meet one of the following criteria: o Platinum-resistant disease or; o Patients refrains from standard therapy or; o Asymptomatic patients who are not yet eligible for standard palliative chemotherapy but have an increase of CA125 tumour marker at two consecutive timepoints 28 days apart with a value of two times nadir above 35 U/ml). - Progressive disease after at least one prior line of systemic treatment for recurrent disease. - Radiologically evaluable disease according to RECIST 1.1 criteria. - Ability and willingness to obtain a tumour biopsy after the last course of standard treatment and before start of the study. - Ability and willingness to provide written and oral consent. - Able to speak and understand the Dutch language. - WHO performance status 0-II. - Adequate renal and liver function to start matched targeted therapy (according to the local clinician). - Adequate use of contraceptives in case of patients with childbearing potential.
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E.4 | Principal exclusion criteria |
- Age < 18 years. - Patient is receiving any other anti-cancer therapy (e.g. cytotoxic or targeted drug or radiation) or is chemotherapy naïve. The required wash out period prior to start of matched targeted therapy is at least three weeks. - Patient is diagnosed with or treated for a second primary tumour (except non-melanoma skin tumour) one year prior to study inclusion. - Inability to obtain (sufficient) tumour material. - Previous use of the selected targeted drug as anti-cancer agent. - Physical condition WHO III-IV. - Pregnant or lactating women. - Simultaneous participation in another treatment-related clinical trial. - Patients with any other clinically significant medical condition which, in the opinion of the local clinician, makes it undesirable for the patient to participate in this study or which could jeopardize compliance with study requirements including, but not limited to: ongoing or active infection, severe psychiatric illness, or complicated social situations. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the progression-free survival (PFS) ratio defined as the PFS on matched targeted therapy by signal transduction activation (STA)-analysis (PFS2) divided by the PFS recorded on the therapy administered prior to enrolment (PFS1). A PFS2/PFS1 ratio ≥ 1.3 in 30% of the included patients is assumed to have meaningful clinical benefit. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS2 is evaluated every 8 weeks by radiological imaging according to RECIST 1.1 criteria. PFS1 is retrospectively determined at the time of enrollment. |
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E.5.2 | Secondary end point(s) |
1. Proportion of patients with an actionable active pathway for which targeted therapy is recommended in relation to the number of patients who underwent a biopsy. 2. Proportion of patients who receive matched targeted therapy in relation to the number of patients included in each study arm (i.e. with recommended targeted therapy). 3. Best overall response defined by RECIST 1.1 criteria. 4. One-year survival and overall survival. 5. Correlation between STA-analysis results (and if available, immunohistochemical biomarker analysis / DNA/RNA sequencing results) and progression-free survival on matched targeted therapy (PFS2). 6. Side effects according to Patient Reported Outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE). 7. Health-related quality of life (HRQoL) scored using standardized questionnaires of the European Organisation for Research and Treatment of Cancer (EORTC). 8. Cost-effectiveness will be calculated with health state utilities assessed in the standardized EuroQol 5D (EQ-5D-5L) questionnaire. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Once a year. 2. Once a year. 3. Every 8 weeks. 4. Once a year. 5. Once a year. 6. Baseline, 2 weeks and 8 weeks after start of therapy. Thereafter every 8 weeks until disease progression and 8 weeks after the therapy was ended. 7. Baseline and 8 weeks after start of therapy. Thereafter every 8 weeks until disease progression and 8 weeks after the therapy was ended. 8. Baseline and 8 weeks after start of therapy. Thereafter every 8 weeks until disease progression and 8 weeks after the therapy was ended. |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To investigate the value of signal transduction activation (STA) analysis in the selection of patients for matched targeted therapy based on signal transduction pathway activity in the tumor. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Standard of care by local clinician |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 6 |
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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The study will end after the last subject has ended the follow-up period for the duration of usage with a minimum of one year. In case of persistent response to matched targeted therapy after one year of follow-up, the follow-up period will be prolonged until progression of disease. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |