A Study of Docetaxel + ARN-509 in Castration-Resistant Prostate Cancer

NCT03093272 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-485
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of drugs as a possible treatment for castration-resistant prostate cancer. The interventions involved in this study are:

• Docetaxel (a type of chemotherapy)
• Apalutamide (the study medication, also known as ARN-509)
• Prednisone (a corticosteroid given to prevent reactions to docetaxel).
• Leuprolide acetate (also known as Lupron, a GnRH agonist or similar drug which is standard of care, causes chemical castration which greatly lowers the level of testosterone in the body)

Conditions

Prostate Cancer

Keywords

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide

  Progression free survival (PFS) is defined as the time from treatment initiation until the occurrence of one of the following: 1. A participant was considered to have progressed by bone scan if 1. the first bone scan with greater than or equal to (≥) 2 new lesions compared to baseline was observed in less than (\<) 12 weeks from study drug initiation and was confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline); 2. the first bone scan with ≥2 new lesions compared to baseline was observed in ≥12 weeks from study drug initiation and the new lesions were verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline); 2. Progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) by RECIST v. 1.1; or 3. Death from any cause.

  Disease was evaluated radiologically at baseline and every 12 weeks on treatment; PFS follow up was up to 9.4 months

Secondary Outcomes (5)

• Number of Participants With Dose-Limiting Toxicities in the Safety Lead-in Group (First 6 Patients)

  First 3 weeks of treatment

• Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis

  Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.

• Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis

  Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.

• Serum PSA Change From Baseline to 12 Weeks on Treatment

  PSA was measured on Cycle 1 Day 1 (Baseline) and at 12 weeks on treatment.

• Overall Survival

  Measured from end of study treatment to death due to any cause; OS measured as 22.4 months

Study Arms (1)

ARN-509 Combined With Docetaxel

EXPERIMENTAL

* Apalutamide (ARN-509) will be taken orally at home daily * Docetaxel will be administered every 3 weeks intravenously * Prednisone will be taken orally twice daily * Leuprolide Acetate will be administered at the specification of the physician

Drug: Leuprolide Acetate; Drug: Prednisone; Drug: Docetaxel; Drug: Apalutamide

Interventions

Leuprolide Acetate DRUG

a GnRH agonist

Also known as: Lupron Injection

ARN-509 Combined With Docetaxel

Prednisone DRUG

Prednisone is a corticosteroid

Also known as: Deltasone

ARN-509 Combined With Docetaxel

Docetaxel DRUG

Docetaxel is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly.

Also known as: Docefrez, Taxotere

ARN-509 Combined With Docetaxel

Apalutamide DRUG

The apalutamide drug substance is an almost white to slightly brown powder. The tablet formulation of apalutamide is an immediate release oral tablet containing 60-mg of drug substance, with a non-functional green film coat

Also known as: ARN-509

ARN-509 Combined With Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Castration-resistant prostate cancer requires the following criteria:
• A castrate level of testosterone (\< 50ng/dL)
• Prostate cancer progression on or since last treatment as documented by PSA rise or bone progression according to PCWG2 or soft tissue radiographic progression according to RECIST criteria Version 1.1
• If on anti-androgen, will need to show no PSA decline after at least a 6 week withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks from last flutamide dose
• Will require a 2 week washout period from last dose of ketoconazole, abiraterone acetate or radiation
• Treatment with abiraterone acetate for CRPC in the past is required. Does not need to be the last treatment prior to enrollment.
• There is no limit to number of prior therapies
• Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A)
• Adequate organ function as evaluated by the following laboratory criteria:
• Hemoglobin ≥ 9g/dL; no transfusions and erythropoietin supplementation permitted within the last 3 months
• Absolute neutrophil count (ANC) ≥ 1500/µL
• Platelet count ≥ 100 x 10\^9/L

You may not qualify if:

• Pathology consistent with majority of specimen having small cell carcinoma of the prostate (prostate cancer with neuroendocrine features is acceptable).
• Prior treatment with enzalutamide for CPRC; non-CRPC use allowed (e.g., neoadjuvant, combined with radiation for localized disease and didn't progress while on it in those settings)
• Prior treatment with docetaxel chemotherapy except if \> 12 months since it was given in either the neoadjuvant or adjuvant setting or for hormone sensitive disease (e.g., CHAARTED population)
• Presence of untreated brain metastasis
• Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). Loss of consciousness within 12 months may be permitted upon discussion with study PI.
• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.
• Current, recent (within 4 weeks of the first dose of this study), or planned participation in an experimental drug study
• Persistent grade \> 1 (NCI CTCAE v4.0) AEs due to investigational drugs that were administered more than 14 days before study enrollment.
• Radiation within 2 weeks prior to entering the study
• Peripheral neuropathy ≥ Grade 2.
• Current evidence of any of the following:
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption
• Active infection (e.g., human immunodeficiency virus \[HIV\] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Uncontrolled intercurrent illness including, but not limited to, severe or unstable angina, myocardial infarction, symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater), arterial or venous thromboembolic events (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias, significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic peripheral vascular disease within 6 months prior to randomization.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide; Prednisone; Docetaxel; apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Lauren Harshman, MD
• Organization: Dana-Farber Cancer Institute

laurenc_harshman@dfci.harvard.edu

617-632-2429

Study Officials

• Lauren C Harshman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 28, 2017
• Study Start: June 23, 2017
• Primary Completion: May 16, 2019
• Study Completion: December 31, 2019
• Last Updated: April 9, 2020
• Results First Posted: March 30, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)