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Prostate CancerPhase 2NCT03093272

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

A Phase 2 study testing Leuprolide Acetate, Prednisone and Docetaxel in people with Prostate Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Leuprolide Acetate, Prednisone and Docetaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
2 sitesUnited States
Study dates
23 Jun 2017to 31 Dec 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Total bilirubin ≤ upper limit of normal (ULN, Note: In subjects with Gilbert's syndrome, if total bilirubin is ≥ 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ ULN, subject may be eligible)
  • AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis
  • Serum creatinine < 2.0 × ULN or creatinine clearance > 30cc/min
  • Serum albumin ≥ 3.0 g/dL
  • Serum potassium ≥ 3.5 mmol/L (if < 3.5, can be repleted and reassess for eligibility as long as stable off potassium supplementation for > 48 hrs)
  • Ability to swallow the study drug as a whole tablet
  • The effects of apalutamide and docetaxel on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, men must agree to use adequate contraception. Specifically, they must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. They must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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.
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Any condition that in the opinion of the investigator, would preclude participation in this study
  • History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80 or antisense oligonucleotides.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to apalutamide or docetaxel
  • Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
  • Inability to comply with study and/or follow-up procedures

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients Post Abiraterone Acetate

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)
Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

Apalutamide is considered an investigational product, which is believed to reduce the growth of prostate cancer cells. The FDA (the U.S. Food and Drug Administration) has not approved apalutamide as a treatment for any disease, but it is being studied in prostate cancer. Docetaxel is an approved therapy for this type of cancer. The FDA has not approved the combination of the two drugs in any use.

In this research study, the investigators are evaluating the combination of two drugs, docetaxel with apalutamide. The investigators will keep track of participants' prostate-specific antigen (PSA), scans, and overall health to determine how well this drug combination works at treating this type of cancer.

Conditions
Prostate Cancer
Being tested
Leuprolide Acetate, Prednisone, Docetaxel, Apalutamide
Keywords
Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leuprolide AcetateDrug

    Also called Lupron Injection

    a GnRH agonist

  • PrednisoneDrug

    Also called Deltasone

    Prednisone is a corticosteroid

  • DocetaxelDrug

    Also called Docefrez, Taxotere

    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.

  • ApalutamideDrug

    Also called ARN-509

    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

Study groups in NCT03093272
Study groupRoleWhat they receive
ARN-509 Combined With DocetaxelExperimental* 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
Receives: Drug: Leuprolide Acetate; Drug: Prednisone; Drug: Docetaxel; Drug: Apalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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
    2. 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);
    3. 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);
    4. Progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) by RECIST v. 1.1; or
    5. Death from any cause.

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

Secondary outcomes (5)

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

    Specific adverse events will be recorded during the safety lead-in phase of 6 patients. Any toxicities considered unacceptable during this time will be considered a dose-limiting toxicity and will be summarized among all patients evaluable for a dose-limiting toxicity (DLT).

    Measured: First 3 weeks of treatment

  2. Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis

    The pharmacokinetic (PK) parameters of the first 9 patients enrolled at Dana-Farber Cancer Institute will be determined using noncompartmental methods with WinNonLin version 5.2. Maximum blood concentration (Cmax) will be determined by visual inspection. Due to the premature termination of the study, only 9 patients were evaluated. The PK samples were collected on Days 1 and 2 of the first two treatment cycles.

    Measured: 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.

  3. Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis

    The area under the blood concentration-time curve (linear trapezoidal rule) will be determined between 0-24 hours (AUC0-24). The PK samples were collected during the first two days of cycles 1 and 2.

    Measured: 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.

  4. Serum PSA Change From Baseline to 12 Weeks on Treatment

    The maximum percent PSA change (rise or fall) from baseline to after 12 weeks on study. For patients who discontinue on or before the 12 week assessment or for whom the 12 week assessment is missing, the last observation prior to the week 12 assessment will be utilized. Patients with no post-baseline PSA data will be excluded from the summary.

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

  5. Overall Survival

    Overall Survival (OS) is defined as the time from trial treatment start to death due to any cause, or censored at date last known alive.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2017
  2. Study start23 Jun 2017
  3. Primary completion16 May 2019
  4. Study completion31 Dec 2019

Why it stopped: Safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03093272
Sponsor's protocol ID
16-485
Status last verified
Apr 2020
First submitted
15 Mar 2017
Last updated
9 Apr 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Leuprolide Acetate, Prednisone and Docetaxel in people with Prostate Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide (time frame: Disease was evaluated radiologically at baseline and every 12 weeks on treatment; PFS follow up was up to 9.4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03093272.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2020.

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