| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced, Platinum-Resistant, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian-Tube Cancer |
|
| 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) |
|
| 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 | 10016180 |
| E.1.2 | Term | Fallopian tube cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 | 10061344 |
| E.1.2 | Term | Peritoneal neoplasm |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 efficacy objective of this study is to evaluate progression-free survival (PFS) by Blinded Independent Central Review (BICR) in patients treated with an intermittent regimen of relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel monotherapy. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives are to evaluate patients treated with an intermittent regimen of relacorilant in combination with nab-paclitaxel compared with nab-paclitaxel monotherapy:
• To evaluate the OS
• To evaluate PFS as assessed by the Investigator or local radiologist.
• To evaluate ORR
• To evaluate BoR
• To evaluate DoR
• To evaluate CBR at 24 weeks
• To evaluate response according to cancer antigen 125 (CA-125) using Gynecologic Cancer Intergroup (GCIG) criteria. A combined-response endpoint based on RECIST v1.1 and GCIG criteria will also be reported. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed and dated Institutional Review Board/Independent Ethics Committee-approved informed consent form prior to study-specific Screening procedures.
2. Female patients aged ≥18 years old at time of consent.
3. Confirmed histologic diagnosis of high-grade (Grade 3) serous, epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (high-grade endometroid epithelial or carcinosarcoma with ≥30% epithelial component are eligible).
4. Patients must have platinum-resistant disease (defined as progression < 6 months (+7 days) from completion of a platinum-containing therapy).
5. Must consent to provide archival tumor-tissue block or slides, if available. Patients may consent to an optional tumor biopsy if archival tumor-tissue is unavailable.
6. Has a life expectancy of ≥3 months.
7. At least one lesion that meets the definition of measurable disease by RECIST v.1.1 (previously irradiated lesions not allowed as measurable disease unless there is documented evidence of progression in the lesions).
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
9. Able to comply with protocol requirements.
10. Able to swallow and retain oral medication and does not have uncontrolled emesis.
11. Received at least 1 but ≤3 lines of prior systemic anticancer therapy (See Protocol for the guidance in counting the number of prior lines of therapy) with documented progressive disease or intolerance to the most recent therapy. At least 1 prior line of platinum therapy is required and prior treatment with bevacizumab is required.
12. Has adequate organ function meeting the protocol-defined laboratory-test criteria.
13. Negative pregnancy test for patients of childbearing potential. Patients of childbearing potential must agree to use highly effective contraceptive method(s); hormonal contraceptives are not allowed.
14. COVID-19 approved vaccines (or vaccines with regulatory health authority’s emergency use authorization / conditional marketing authorization) are accepted concomitant medications when recommended by the Investigator. Exceptions may apply should the Investigator and the Medical Monitor determine that the vaccine will interfere with the objectives of the study.
Please refer to the protocol for complete list of inclusion criteria. |
|
| E.4 | Principal exclusion criteria |
1. Has clinically relevant and reversible toxicity from prior systemic anticancer therapies or radiotherapy that has not resolved to ≤Grade 1 prior to randomization.
2. Has had any major surgery within 4 weeks prior to randomization. If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the study treatment.
3. Has low-grade serious or endometrioid histology other than epithelial, or clear cell, or mucinous, or sarcomatous with less than 30% epithelial histology component, or mixed tumors containing any of these histologies, or borderline ovarian tumor.
4. Has primary platinum-refractory disease, defined as disease that did not respond to, or has progressed during or within ≤ 1 month from completion of a platinum-containing chemotherapy in first-line treatment (measured from the date of the last dose of platinum).
5. Has not received prior bevacizumab treatment.
6. Has been treated with the following prior to randomization:
− Chemotherapy, immunotherapy, investigational agent etc. treatments for disease under study within 5 times of half-life of the prior therapy, or 28 days if 5 times the half-life of the prior therapy is longer than 28 days, before the first dose of study drug.
− Radiotherapy not completed at least 2 weeks prior to first dose of study drug.
− Hormonal anticancer therapies within 7 days of first dose of study drug.
− Systemic, inhaled, or prescription strength topical corticosteroids within a period equivalent to 5 times the half-life of the corticosteroid used prior to first dose of study drug.
7. Has received wide-field radiation to more than 25% of marrow-bearing areas.
8. Has toxicities of prior therapies that are reversible and have not resolved the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, ≤Grade 1.
9. Requires treatment with chronic or frequently used oral corticosteroids for medical conditions or illnesses (e.g., rheumatoid arthritis, immunosuppression after organ transplantation).
10. Has a history of severe hypersensitivity or severe reaction to any of the study drugs.
11. Is receiving concurrent treatment with mifepristone or other glucocorticoid receptor (GR) modulators.
12. Has peripheral neuropathy from any cause > Grade 1.
13. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial, starting with the Screening visit through at least 6 months after the last dose of study treatment.
14. Has clinically significant uncontrolled condition(s) which, in the opinion of the Investigator, may confound the results of the trial or interfere with the patient’s safety or participation.
15. Has current active (chronic/acute) infection with Human immunodeficiency virus, or hepatitis C virus or hepatitis B virus.
16. Has any untreated or symptomatic central nervous system (CNS) metastases.
17. Patients with a history of other malignancy within 3 years prior to randomization.
18. Is taking a prohibited concomitant medication listed in protocol (some of the prohibited concomitant medications listed may require a washout period prior to the first dose of study drug).
19. Concurrent treatment on other investigational treatment studies for ovarian, fallopian-tube, or primary peritoneal cancer.
20. Has received a live vaccine within 30 days prior to the study start date.
Please refer to the protocol for complete list of exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy study endpoint will be PFS defined as the time from randomization until first documented progressive disease (PD) by RECIST v1.1 per BICR, or death due to any cause, whichever occurs first. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| As defined in the end point |
|
| E.5.2 | Secondary end point(s) |
• OS: Time from randomization to death by any cause.
• PFS (Investigators): Time from randomization until PD or death whichever occurred first as assessed by Investigator using RECIST v1.1.
• ORR: Proportion of patients with measurable disease at Baseline who attain complete response (CR) or partial response (PR) by RECIST v1.1.
• BoR: Recorded from the date of randomization until PD/recurrence (or death).
• DoR: Time from the first objective response (CR or PR) to first objectively documented PD or death (whichever occurs first).
• CBR at 24 weeks: proportion of patients who attain CR, PR, or stable disease (SD) for 24 weeks as per RECIST v1.1.
• CA-125 response will be assessed per GCIG criteria
• Combined response according to RECIST v1.1 + GCIG criteria. Responses will be reported separately and combined for RECIST v1.1 and CA-125/GCIG criteria. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| As defined in the endpoint |
|
| 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 | 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 |
Patient-Reported Outcomes and Quality of Life
Biomarkers |
|
| 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 | 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) | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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 |
| Argentina |
| Australia |
| Brazil |
| Canada |
| Israel |
| Korea, Republic of |
| United Kingdom |
| United States |
| Belgium |
| France |
| Hungary |
| Italy |
| Poland |
| Spain |
|
| 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
|
| The end of study is defined as the date of last contact (i.e., visit, telephone, e-mail) with the last patient in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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