Clinical trial NCT04329949: Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
Official title: A Phase 3 Study of Relacorilant in Combination With Nab-Paclitaxel in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (RELIANT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Pancreatic Ductal Adenocarcinoma
Keywords: Pancreatic Cancer
mPDAC
Metastatic Pancreatic Ductal Adenocarcinoma
Glucocorticoid Receptor
Nab-paclitaxel
GR Antagonist
Relacorilant
Abraxane
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-04-01
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, open-label study to evaluate the objective response rate (ORR), in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with relacorilant in combination with nab-paclitaxel, according to blinded independent central review.

Detailed description: Relacorilant is a small-molecule antagonist of the glucocorticoid receptor (GR). The goals of this study are to evaluate the efficacy, safety, and pharmacokinetics (PK) of relacorilant in combination with nab-paclitaxel in the treatment of metastatic pancreatic ductal adenocarcinoma.

Eligible patients are those with mPDAC who have received at least 2 prior lines of therapy for pancreatic ductal adenocarcinoma in any setting, including at least 1 prior gemcitabine-based therapy and at least 1 prior fluoropyrimidine-based therapy.

Patients will receive treatment until progressive disease (PD) (per RECIST v1.1) as determined by the Investigator, experiencing unmanageable toxicity, or until other treatment discontinuation criteria are met. All patients will be followed for documentation of disease progression and survival information (i.e., date and cause of death) and subsequent treatment.

Eligibility criteria: Inclusion Criteria - Patients must have the following:

Histologically confirmed PDAC with metastatic disease

Received at least 2 prior lines of therapy for PDAC in any setting, including at least 1 prior gemcitabine-based therapy and at least 1 prior fluoropyrimidine-based therapy

Received no more than 4 prior lines of cytotoxic or myelosuppressive therapy for PDAC

A measurable lesion at baseline (within 21 days prior to the first dose of relacorilant) per RECIST v1.1, as assessed by the Investigator

Willingness to provide blood samples and tumor tissue (primary or metastatic) for research purposes

Karnofsky performance status (KPS) score of ≥70

Adequate gastrointestinal absorption. If the patient has undergone gastric bypass surgery and/or surgery of gastrointestinal or hepatobiliary tract, the patient must demonstrate adequate absorption as evidenced by albumin ≥3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of evidence of malabsorption

Adequate organ and marrow function (determined through blood and urine tests)

Exclusion Criteria - Patients must not have the following:

Pancreatic neuroendocrine tumors, lymphoma of the pancreas, acinar pancreatic cancer, or ampullary cancer

Known untreated parenchymal brain metastasis or have uncontrolled central nervous system metastases. Patients must not require steroids and must be neurologically stable without corticosteroids for a minimum of 3 weeks prior to Cycle 1 Day 1

Clinically relevant toxicity from prior systemic cytotoxic therapies or radiotherapy that in the opinion of the Investigator has not resolved to Grade 1 or less prior to enrollment, including peripheral neuropathy that is ongoing and greater than Grade 1 in severity, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0

History of hypersensitivity or severe reaction to either relacorilant or nab-paclitaxel, or to similar classes of either drug

Taken the following medications prior to enrollment:

1. An investigational product, cytotoxic chemotherapy, or targeted agent within 14 days
2. Radiotherapy within 21 days
3. Palliative radiotherapy within 1 week of Cycle 1 Day 1, or if toxicities from radiotherapy are Grade 2 severity or higher or have not recovered to baseline
4. Systemic or prescription-strength topical corticosteroids for the purposes of treating a chronic nononcologic indication within 21 days.

Requirement for treatment with chronic or frequently used oral or inhaled corticosteroids for medical conditions or illnesses (e.g., rheumatoid arthritis, asthma, or immunosuppression after organ transplantation)

Taking a concomitant medication that is a strong CYP3A (cytochrome P450 3A) or CYP2C8 inhibitor or inducer, or a substrate of CYP3A or CYP2C8 and has a narrow therapeutic window

Concurrent treatment with mifepristone or other GR antagonists

Any clinically significant uncontrolled condition(s) or any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities or impair study participation or cooperation

Any major surgery within 21 days prior to enrollment

Endoscopic retrograde cholangiopancreatography with persistence of any of the following:

1. Bilirubin ≥1.5 × ULN (Upper Limit of Normal)
2. Amylase \>2 × ULN and abdominal pain or amylase \>3 × ULN (with or without symptoms)
3. Fever or signs of infection
4. Decreasing hemoglobin or signs of blood loss.

A history of human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). (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 results may be performed and must be negative for enrollment.)

A rapid decline in KPS score or serum albumin (≥20%), or have progressive pain symptoms indicative of rapid clinical deterioration, in the opinion of the Investigator, prior to enrollment. These patients will become ineligible if rapid decline is observed during the screening period.

Primary outcomes:
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
timeFrame: Baseline and up to 32 weeks
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Investigator Assessment
timeFrame: Baseline and up to 48 weeks
measure: Best Overall Response (BOR)
timeFrame: Baseline and up to 32 weeks
measure: Duration of Response (DOR)
timeFrame: Time of response up to 32 weeks
measure: Disease Control Rate (DCR)
timeFrame: Enrollment through 18 weeks
measure: Progression-Free Survival (PFS)
timeFrame: Baseline and up to 31 weeks.
measure: Overall Survival (OS)
timeFrame: Baseline and up to 70 weeks
measure: Progression-Free Survival (PFS)
timeFrame: Enrollment through 3 months, 6 months, and 12 months
measure: Overall Survival (OS)
timeFrame: Enrollment through 3 months, 6 months, and 12 months
measure: Cancer Antigen (CA)19-9
timeFrame: Enrollment through 8 weeks and 16 weeks
measure: Tumor Response Per European Organization for Research and Treatment of Cancer (EORTC) Criteria
timeFrame: Enrollment through 6 weeks
measure: Time to Progression (TTP)
timeFrame: Baseline and up to 32 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Site #038
state: Arizona
city: Duarte
country: United States
facility: Site #171
state: California
city: Los Angeles
country: United States
facility: Site #076
state: California
city: Aurora
country: United States
facility: Site #032
state: Colorado
city: Atlanta
country: United States
facility: Site #009
state: Georgia
city: Goshen
country: United States
facility: Site #184
state: Indiana
city: Baltimore
country: United States
facility: Site #065
state: Maryland
city: Detroit
country: United States
facility: Site #058
state: Michigan
city: Omaha
country: United States
facility: Site #185
state: Nebraska
city: Buffalo
country: United States
facility: Site #182
state: New York
city: New York
country: United States
facility: Site #044
state: New York
city: New York
country: United States
facility: Site #222
state: New York
city: Columbus
country: United States
facility: Site #077
state: Ohio
city: Toledo
country: United States
facility: Site #186
state: Ohio
city: Pittsburgh
country: United States
facility: Site #172
state: Pennsylvania
city: Knoxville
country: United States
facility: Site #175
state: Tennessee
city: Nashville
country: United States
facility: Site #176
state: Tennessee
city: Seattle
country: United States
facility: Site #173
state: Washington
Study officials:
affiliation: Corcept Therapeutics, Menlo Park, CA 94025
name: William Guyer, PharmD
role: STUDY_DIRECTOR
References: