| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal 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 objective is to evaluate progression-free survival (PFS) in patients treated with intermittent or continuous regimens of relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel alone. |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy
*To evaluate objective response rate (ORR)
*To evaluate duration of response (DoR)
*To assess response according to cancer antigen 125 (CA-125) using GCIG criteria. A combined response endpoint based on RECIST v1.1 and GCIG will also be reported.
*To evaluate PFS rate at 6 and 12 months
*To evaluate overall survival (OS)
*To evaluate PFS, ORR, DoR and best overall response (BoR) in patients who receive continuous relacorilant in combination with nab-paclitaxel following progression on nab-paclitaxel (crossover)
* To assess response according to CA-125 using GCIG criteria in patients who crossover to continuous relacorilant+nab-paclitaxel
Safety
*To assess the safety of relacorilant treatment in combination with nab-paclitaxel
*To model the exposure-toxicity and exposure-response of relacorilant and nab-paclitaxel in each treatment arm to recommend a dosing regimen of relacorilant in combination with nab-paclitaxel
Pharmacokinetics
*To assess (PK) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed and dated IRB/IEC-approved informed consent form (ICF) prior to study-specific screening procedures.
2. Female patients aged ≥ 18 years old at time of consent.
3. Histologic diagnosis of high grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer or ovarian carcinosarcoma. Clear cell, mucinous and borderline histologic subtypes are excluded.
4. Received at least one line of therapy with progression within 6 months after platinum-based therapy, persistent disease at the completion of primary platinum-based therapy, or PD during platinum-based therapy. Patients with primary platinum resistance (progression after first-line chemotherapy) are considered eligible.
5. Measurable or non-measurable disease by RECIST v1.1:
Previously irradiated lesions are not allowed as measurable disease, unless there is documented evidence of progression in the lesions.
To be eligible with non-measurable disease, patients must have evaluable disease with CA-125 of at least twice the upper limit of the reference range (or CA-125 ≥ 70 U/mL) along with radiographically evaluable disease by CT/MRI.
6. Availability and consent to provide tumor tissue for GR immunohistochemistry (archival or recent biopsy).
7. Up to 2 prior chemotherapeutic or myelosuppressive regimens for recurrent disease (not including maintenance therapy such as single-agent bevacizumab).
8.Appropriate to treat with nab-paclitaxel, in the opinion of the Investigator.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
10. Adequate organ and bone marrow function meeting the following criteria at the Screening Visit:
Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3.
Platelet count ≥ 100,000/mm3.
Hemoglobin ≥ 9 g/dL.
AST or ALT ≤ 2.5 × upper limit of normal (ULN) (or ≤ 5 × ULN in the context of liver metastasis).
Total bilirubin ≤ 1.5 × ULN.
Serum creatinine ≤ 1 × ULN; creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
Albumin ≥ 3 g/dL (≥ 30 g/L) .
11. If patient has undergone surgery of the gastrointestinal or hepatobiliary tract, adequate absorption as evidenced by: albumin ≥ 3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of malabsorption.
12. Able to swallow and retain oral medication and does not have uncontrolled emesis.
13. Able to comply with protocol requirements.
14. Negative pregnancy test for patients of childbearing potential. Patients of childbearing potential must use appropriate precautions to avoid pregnancy, defined as of nonchildbearing potential (i.e., postmenopausal or permanently sterilized) or using highly effective contraception with low user-dependency, for at least 3 months after the last dose of study drug. A woman is postmenopausal if it is more than 12 months since her last menstruation, without an alternative medical cause. Accepted methods of permanent sterilization methods are hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy. Accepted methods of highly effective contraception with low user-dependency are:
An IUD, provided that the subject has tolerated its use for at least 3 months before the first dose of study medication and undertakes not to have it removed for 1 month after the last dose.
Abstinence from heterosexual intercourse, when it is in line with the subject’s preferred and usual lifestyle. Periodic abstinence and withdrawal is NOT acceptable.
Vasectomized partner provided that the partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success.
Oral hormonal contraceptives are NOT permitted. |
|
| E.4 | Principal exclusion criteria |
1. Clinically relevant toxicity from prior systemic anticancer therapies or radiotherapy that in the opinion of the Investigator has not resolved to Grade 1 or less prior to randomization.
2. Any major surgery within 4 weeks prior to randomization. If subject received major surgery including (curative or palliative surgery), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
3. Treatment with the following prior to randomization:
Concurrent treatment with other anticancer therapy including other chemotherapy, immunotherapy, radiotherapy, chemo-embolization, targeted therapy, an investigational agent or the non-approved use of a drug or device within 28 days before the first dose of study drug.
Hormonal anticancer therapies within 7 days of the first dose of study drug.
Systemic, inhaled, or prescription strength topical corticosteroids within 21 days of the first dose of study drug. Short courses (≤ 5 days) for non-cancer-related reasons are allowed if clinically required (such as prophylaxis for CT).
4. Received radiation to more than 25% of marrow-bearing areas.
5. Toxicities of prior therapies (except alopecia) that have not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 ≤ Grade 1.
6. Requirement for treatment with chronic or frequently used oral corticosteroids for medical conditions or illnesses (e.g., rheumatoid arthritis, immunosuppression after organ transplantation).
7. History of severe hypersensitivity or severe reaction to either study drug.
8. Peripheral neuropathy from any cause > Grade 1.
9. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial, starting with screening visit through 90 days after the last dose of trial treatment.
10. Human immunodeficiency virus or current chronic/active infection with hepatitis C virus or hepatitis B virus, including:
Patients with chronic or active hepatitis B as diagnosed by serologic tests are excluded from the study. In equivocal cases, hepatitis B or C polymerase chain reaction may be performed and must be negative for enrollment.
11. Patient has a clinically significant uncontrolled condition(s) or which in the opinion of the Investigator may confound the results of the trial or interfere with the patient’s participation, including but not limited to:
Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months before study entry.
Uncontrolled hypertension (sustained systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg despite optimal management). Patients will be considered eligible if hypertension is treated and controlled during Screening.
Active infection that requires parenteral antibiotics.
Bowel obstruction or gastric outlet obstruction.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. Untreated parenchymal central nervous system metastases.
13. Any other concurrent cancer or a history of another invasive malignancy within the last 3 years that has a likelihood of recurrence of > 30% within the next 5 years. Adequately treated non-melanoma skin cancers or non-muscle invasive urothelial cancer or other tumors curatively treated with no evidence of disease are permissible.
14. Drugs with a narrow therapeutic ratio that are highly dependent on CYP3A for clearance should be avoided. Caution should be exercised when co-administering known inhibitors of CYP3A with relacorilant. Medicines/food known to strongly inhibit CYP3A should be avoided.
15. Concurrent treatment on other investigational treatment studies for the treatment of ovarian, fallopian tube, or primary peritoneal cancer.
16. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression free survival: the time from the date of randomization until the date of first documented PD by RECIST v1.1, (as determined by the Investigator at the local site) or death due to any cause, whichever occurs first |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Every 8 weeks (± 7 days) from Cycle 1, Day 1 irrespective of treatment delays until unequivocal PD is documented, including in patients who discontinue treatment prematurely. |
|
| E.5.2 | Secondary end point(s) |
• ORR: proportion of patients with measurable disease at baseline who attain complete response (CR) or partial response (PR) by RECIST 1.1 (confirmation not required).
• DoR: time from when response (CR or PR) was first documented to first objectively documented PD or death (whichever occurs first)
• BoR: the best response recorded from the date of randomization until PD/recurrence (or death).
• CA-125 response will be assessed per GCIG criteria (Rustin 2011) defined as ≥50% reduction in CA-125 from a pre-treatment sample and maintained for ≥28 days in patients with a pretreatment sample that is at least twice the upper limit of the reference range and within 2 weeks before starting the treatment. In addition, patients who have a CA-125 response and whose CA 125 level falls to within the reference range will be classified as CA -125 complete responders.
• Combined response according to RECIST v1.1 + GCIG criteria. Response will be reported separately and combined for RECIST 1.1 and CA-125/GCIG criteria.
• Progression-free rate (proportion of patients who have not progressed) at 6 and 12 months
• PFS, ORR, DoR, BoR in patients who crossover to the continuous treatment regimen of relacorilant in combination with nab-paclitaxel from the time of PD (baseline for combination therapy) on nab-paclitaxel alone.
• Overall survival: time from randomization to death by any cause. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Assessment using the appropriate response criteria per disease at the time points shown in Table 9 of the protocol |
|
| 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 | No |
| 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 | 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 | Yes |
| 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 | 3 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 |
| Belgium |
| Canada |
| Germany |
| Italy |
| Spain |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 43 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 43 |
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