Study of Relacorilant in Combination With Nab-Paclitaxel for Patients With Recurrent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Summary

This is a Phase 2, open-label, randomized, 3-arm study to evaluate progression-free survival (PFS) in patients with recurrent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer treated with intermittent or continuous regimens of relacorilant in combination with nab-paclitaxel compared with patients treated with nab-paclitaxel alone.

Key Facts

Interventions

Conditions

Eligibility

Inclusion Criteria:

* Signed and dated Investigational Review Board/Independent Ethics Committee-approved informed consent form (ICF) prior to study-specific screening procedures.
* Female patients aged ≥18 years old at time of consent
* 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.
* Received at least 1 line of therapy with evidence of cancer progression within 6 months after the last dose of platinum-based therapy (ie, having a platinum-free interval of ≤6 months \[platinum resistant\]), or progressive disease during or immediately after primary platinum-therapy, (ie, platinum refractory). Patients with primary platinum resistance (progression within 6 months of the last dose of first-line platinum-containing chemotherapy) are considered eligible.

Notes: For the calculation of the platinum-free interval, cancer progression must be defined by clear evidence of progression, such as radiographic progression per RECIST v1.1. Calculating the platinum-free interval on the basis of increased Cancer Antigen (CA-125) is not allowed.

* 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 at least twice the upper limit of reference range (of CA-125 ≥70 U/mL), along with radiographically evaluable disease by computerized tomography (CT)/magnetic resonance imaging (MRI).
* Availability and consent to provide tumor tissue for biomarker assays (archival or recent biopsy).
* No more than 4 prior chemotherapeutic or myelosuppressive regimens (not including maintenance therapy such as single-agent bevacizumab or poly (ADP-ribose) polymerase \[PARP\] inhibitors). Patients with platinum-refractory cancer cannot have had more than 2 prior lines of treatment for refractory disease.
* Appropriate to treat with nab-paclitaxel, in the opinion of the Investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Adequate organ and bone marrow function meeting the following criteria at the Screening Visit:

  * Absolute neutrophil count (ANC) ≥1,500 cells/mm\^3.
  * Platelet count ≥100,000/mm\^3.
  * Hemoglobin ≥9 g/dL.
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) (or ≤5 × ULN in the context of liver metastasis).
  * Total bilirubin ≤1.5 × ULN.
  * Creatinine clearance ≥45 mL/min/1.73 m\^2 (measured or estimated).
  * Albumin ≥3 g/dL (≥30 g/L) .
* 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.
* Able to swallow and retain oral medication and does not have uncontrolled emesis.
* Able to comply with protocol requirements.
* Negative pregnancy test for patients of childbearing potential. Patients of childbearing potential must use appropriate precautions to avoid pregnancy, defined as of non-childbearing potential (ie, postmenopausal or permanently sterilized) or using highly effective contraception with low user-dependency, for at least 3 months after the last dose of relacorilant, or per the duration indicated in the product label for nab-paclitaxel, whichever is latest. 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 intrauterine device (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 are 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.

Exclusion Criteria:

* 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.
* 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.
* Treatment with the following prior to randomization:

  * Concurrent treatment with other anticancer therapy including other chemotherapy, immunotherapy, radiotherapy, chemoembolization, 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).
* Received radiation to more than 25% of marrow-bearing areas.
* 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.
* Requirement for treatment with chronic or frequently used oral corticosteroids for medical conditions or illnesses (eg, rheumatoid arthritis, immunosuppression after organ transplantation).
* History of severe hypersensitivity or severe reaction to either study drug.
* Peripheral neuropathy from any cause \>Grade 1.
* 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 3 months after the last dose of relacorilant, or per the duration indicated in the product label for nab-paclitaxel, whichever is latest.
* 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.
* 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.
* Untreated parenchymal central nervous system metastases.
* 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.
* Are taking a concomitant medication that is a strong CYP3A inhibitor or inducer, or that is a substrate of CYP3A with a narrow therapeutic window.
* Concurrent treatment with mifepristone or other glucocorticoid receptor (GR) antagonists.
* Concurrent treatment on other investigational treatment studies for the treatment of ovarian, fallopian tube, or primary peritoneal cancer.
* 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.

Outcome Measures

Locations

Linked Papers

Linked Investigators