Clinical trial NCT04325828: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma
Official title: An Open-label Phase 2 Study to Evaluate the Efficacy and Safety of Apalutamide in Combination With Gonadotropin-releasing Hormone (GnRH) Agonist in Subjects With Locally Advanced or Recurrent/Metastatic and Androgen Receptor (AR) Expressing Salivary Gland Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Salivary Gland Neoplasms
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2020-03-30
Enrollment: 31
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: The purpose of the study is to evaluate the overall response rate (ORR) of apalutamide in combination with a gonadotropin-releasing hormone (GnRH) agonist in participants with androgen receptor (AR) expressing locally advanced or recurrent/metastatic salivary gland carcinoma (SGC).


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed salivary gland carcinoma (SGC) by local pathology
* Androgen receptor (AR) expressing SGC: Local testing of AR-positivity will be performed as standard of care for the eligibility confirmation. AR-positivity will be defined according to immunohistochemistry (IHC) staining of tumor tissue with at least 1 percent (%) of cell nuclei staining positive. Tissue should be available for the central confirmation of AR-positivity, but the central result of AR positivity will not be required for initiating the study intervention
* Locally advanced or recurrent/metastatic SGC
* Measurable lesion(s) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

* Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to first dose. Treatment with a drug that has a short half life (t1/2) (for example, less than \[\<\] 1 day) may be eligible in accordance with the discussion with the sponsor's medical monitor
* Radiographically confirmed brain metastases. In case of history of brain metastases that were previously treated and not recurred for at least 6 months, they are considered eligible
* Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less (except for all grade alopecia, and for peripheral neuropathy, and hypothyroidism stable on hormone replacement therapy to be Grade 2 or less). If corticosteroids are administered for any reasons such as the management of toxicities due to prior therapies, the dose must be tapered until 10 milligram (mg)/day or less of prednisolone and contact the sponsor's medical monitor on an individual basis prior to the first dose
* Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
* History of seizure or any condition that may predispose to seizure (including, but not limited to, prior stroke, transient ischemic attack, or loss of consciousness less than or equal to \[\<=\] 1 year prior to first dose; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
* Treatment with drugs known to lower the seizure threshold within 4 weeks prior to first dose
* Known or suspected contraindications or hypersensitivity to apalutamide, gonadotropin-releasing hormone agonist (GnRHa) analogues or any of the components of the formulations
* Received prior ADT including a GnRH analogue, AR blocker such as bicalutamide, enzalutamide or 17alpha-hydroxylase-17,20-lyase (CYP17) inhibitor such as abiraterone acetate etc. Chemotherapy, radiation, or surgery as part of curative intent therapy are allowed so long as prior therapy did not include ADT. Prior chemotherapy, targeted cancer therapy or immunotherapy within 1 week or 4 half-lives whichever is longer, before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 2 weeks

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 13 months
Secondary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 13 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 13 months
measure: Progression-free Survival (PFS) as Assessed by ICRR
timeFrame: Up to 13 months
measure: Overall Survival (OS)
timeFrame: Up to 13 months
measure: Time to Response (TTR)
timeFrame: Up to 13 months
measure: Duration of Response (DoR)
timeFrame: Up to 13 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 13 months
measure: Plasma Concentration of Apalutamide
timeFrame: Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)
measure: Plasma Concentration of N-desmethyl Apalutamide
timeFrame: Day 1 (predose) of Cycles 2 to 6 (each cycle was of 28 days)
Other outcomes:
Locations:
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Medical Center
city: Hirakata City
country: Japan
facility: Kansai Medical University Hospital
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Nagoya Shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Niigata
country: Japan
facility: Niigata University Medical And Dental Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: