Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily. Once Recommended Phase 2 Dose (RP2D) has been selected, Phase 1 participants being treated at the lower dose levels will be allowed to escalate to the RP2D level at the discretion of the primary investigator.

Participants with non-metastatic, treatment-naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) will be enrolled. ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.

Participants with treatment-naive metastatic CRPC will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

Participants with metastatic CRPC that are chemotherapy-naive, but have been previously treated with abiraterone will be enrolled. ARN-509 will be administered at MTD and/or RP2D, determined in Phase 1.

ARN-509 will be administered at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily.

ARN-509 (Phase 1)

ARN-509 will be administered at Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), determined in Phase 1.

ARN-509 (Phase 2)

Aragon Pharmaceuticals, Inc Clinical Trial

The purpose of this study is to assess the safety and activity of ARN-509 in men with advanced castration resistant prostate cancer. Patients will first be enrolled into Phase 1 of the study to identify a tolerable dose for the Phase 2 portion of the study. In the Phase 2, 3 different cohorts of patients will be enrolled to evaluate the safety and activity of ARN-509.

Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

An Open-Label, Phase 1/2, Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 in Patients With Progressive Advanced Castration-Resistant Prostate Cancer

Percentage of participants with \>=50% decrease in PSA compared to baseline were assessed at Week 12. PSA progression was defined by the protocol-specific Prostate Cancer Working Group 2 (PCWG2) criteria: PSA increase greater than or equal to \[\>=\] 25 percent \[%\] and \>=2 nanogram per milliliter \[ng/mL\] above the nadir confirmed \>=3 weeks later; or \>=25% and \>=2 ng/mL above baseline PSA after 12 weeks.

Time to PSA progression was measured as the time interval from the date of the first dose to the date of PSA progression as defined by the PCWG2 criteria. PCWG2 criteria: For participants who achieved \>=50% decrease from the baseline PSA, assessment of time to disease progression was when the PSA increased 25% and at a minimum of 2 ng/mL above the nadir at 3 or more weeks later. For participants without a PSA decrease, the time for progression was calculated at the time when the PSA progression was \>=25% and \>=2 ng/mL after 12 weeks.

MFS was defined as the time from the start of treatment until new metastatic lesions were observed on Computed Tomography/ Magnetic Resonance Imaging (CT/MRI) scans or radionuclide bone scans (according to PCWG2 criteria: appearance of \>=2 new lesions, and, for the first reassessment only, a confirmatory scan performed 6 or more weeks later that showed at least 2 or more additional new lesions) or death, whichever occurred first.

PFS was defined as the time from randomization to the radiographic disease progression or death, whichever occurred first. Radiographic progression defined by at least one of the following: a) Soft tissue progression by modified RECIST confirmed on repeat imaging \>= 6 weeks later; b) Progression by bone scans: 1) first bone scan with \>= 2 new lesions compared to baseline observed \<12 weeks from start date and confirmed on a second bone scan \>=6 weeks later that showed \>=2 additional lesions (a total of \>=4 new lesions compared to baseline); or 2) first bone scan with \>=2 new lesions compared to baseline observed \>=12 weeks from start date and the new lesions verified on the next bone scan \>=6 weeks later (a total of \>=2 new lesions compared to baseline).

Objective Response Rate was defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors, Version 1.0 (RECIST). Where, CR defined as disappearance of all target lesions. Any pathological lymph nodes must had reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions. Confirmed responses were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response.

Aragon Pharmaceuticals, Inc.

Safety population included all participants who received at least one dose of apalutamide.

Participants received apalutamide at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.

Dose Escalation Cohort (Phase 1)

Participants with non-metastatic, treatment naive Castration-Resistant Prostate Cancer (CRPC) with rapidly rising Prostate Specific Antigen (PSA) enrolled in Cohort 1 of Phase 2, received apalutamide at Maximum Tolerated Dose (MTD) and/or RP2D of 240 mg, determined in Phase 1.

Cohort 1: Non-metastatic CRPC (Phase 2)

CRPC (Phase 2) Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatmentnaive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.

Cohort 2: Treatment-naive Metastatic CRPC (Phase 2)

Participants with metastatic CRPC that were chemotherapynaive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.

Cohort 3: Post-Abiraterone Metastatic CRPC (Phase 2)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

These results are up to clinical cutoff (CCO) date 31 March 2017.

Senior Medical Director, WC Clinical Oncology Department

Participants with metastatic CRPC who had not received chemotherapy for metastatic disease or prior abiraterone acetate (treatment-naive) were enrolled in Cohort 2 of Phase 2, received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.

Participants with metastatic CRPC that were chemotherapy-naive, but had been previously treated with abiraterone acetate enrolled in Cohort 3 of Phase 2 received apalutamide at MTD and/or RP2D of 240 mg, determined in Phase 1.

Modified intent-to-treat (mITT) population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Phase 1 and 2: Percentage of Participants With Greater Than or Equal to (>=) 50 Percent (%) Reduction in Prostate-Specific Antigen (PSA) at Week 12

mITT population included all participants who received at least one dose of apalutamide and who were eligible for the cohort that they were enrolled in.

Phase 1 and 2: Median Time to PSA Progression

mITT population included all participants who received at least 1 dose of apalutamide and were eligible for cohort that they were enrolled in. MFS results are reported for Cohort 1 (Phase 2) participants only as MFS analysis was not performed for other cohorts that is Dose Escalation Cohort (Phase 1) and Cohort 2, 3 (Phase 2) per planned analysis.

Phase 2: Median Metastasis-Free Survival (MFS)

mITT population included all participants who received at least 1 dose of apalutamide and who were eligible for cohort that they were enrolled in. PFS results are reported for Dose Escalation Cohort (Phase 1) and cohort 2, 3 (Phase 2) as no PFS analysis was performed for Cohort 1 of Phase 2 per planned analysis.

Phase 1 and 2: Progression-free Survival (PFS)

Phase 1 and 2: Objective Response Rate

Participants received apalutamide (ARN-509) at a starting dose of 30 milligram per day (mg/day), with escalations to 60 mg, 90 mg, 120 mg, 180 mg, 240 mg, 300 mg, 390 mg, and 480 mg daily (up to 240 mg once daily and at higher doses of 300/390/480 mg twice daily dosing). Once Recommended Phase 2 Dose (RP2D) was selected, Phase 1 participants being treated at the lower dose levels were allowed to escalate to the RP2D level (240 mg) at the discretion of the primary investigator.

Spots Global Cancer Trial Database for Safety, Pharmacokinetic and Proof-of-Concept Study of ARN-509 (Apalutamide) in Castration-Resistant Prostate Cancer (CRPC)

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Study Description

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