Apalutamide With or Without Stereotactic Body Radiation Therapy in Treating Participants With Castration-Resistant Prostate Cancer (PILLAR)

STATUS

Recruiting
End date

Dec 31, 2024
participants needed

60
sponsor

University of California, San Francisco

Send

Updated on 8 September 2021

See if I qualify

ct scan

gonadotropin

androgens

direct bilirubin

endocrine therapy

glomerular filtration rate

major surgery

testosterone

neutrophil count

hormone therapy

tumor cells

blood transfusion

docetaxel

antiandrogen therapy

bone scan

bicalutamide

flutamide

antiandrogens

nilutamide

abiraterone

enzalutamide

luteinizing hormone

apalutamide

denosumab

cancer treatment

adenocarcinoma

adenocarcinoma of prostate

darolutamide

Summary

This phase II trial studies the how well apalutamide with or without stereotactic body radiation therapy work in treating participants with castration-resistant prostate cancer. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. It is not yet known whether giving apalutamide with or without stereotactic body radiation therapy works better in treating participants with castration-resistant cancer.

Description

PRIMARY OBJECTIVE:

I. To demonstrate whether the proportion of patients with an undetectable serum prostate specific antigen (PSA) at 6 months following cessation of apalutamide is higher with addition of stereotactic body radiation therapy (SBRT) to prostate specific membrane antigen (PSMA)-avid oligometastatic sites of disease compared to the group of patients receiving apalutamide monotherapy

SECONDARY OBJECTIVES:

I. To compare the time to PSA progression by Prostate Cancer Working Group (PCWG) criteria between treatment arms.

II. To evaluate the safety and tolerability of apalutamide in combination with SBRT.

EXPLORATORY OBJECTIVES:

I. To evaluate the genomic factors associated with the presence of oligometastatic disease via exome sequencing.

II. To evaluate the association between somatic and germline genomic alterations including but not limited to androgen receptor (AR) amplification and point mutations and alterations in deoxyribonucleic acid (DNA) damage response pathway with outcomes on protocol therapy.

III. To characterize the metastatic pattern at baseline and at progression in these patients and to determine whether features of the baseline PSMA-positron emission tomography (PET) scan are associated with treatment outcomes.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive apalutamide orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Beginning 60 days after first dose of apalutamide, participants also undergo stereotactic body radiation therapy for 1-5 fractions.

ARM II: Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed at for 30 days.

Details

Condition	Stage IV Prostate Adenocarcinoma AJCC v7, Castration-Resistant Prostate Carcinoma, Castration Levels of Testosterone, PSA Progression
Treatment	stereotactic body radiation therapy, Apalutamide
Clinical Study Identifier	NCT03503344
Sponsor	University of California, San Francisco
Last Modified on	8 September 2021

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Histologically or cytologically confirmed adenocarcinoma of the prostate
	Progressive, castration-resistant prostate cancer demonstrated during continuous antiandrogen therapy (ADT), defined as 3 PSA rises at least 1 week apart, with a minimum PSA > .05 ng/mL obtained during screening
	At least one but no more than 5 discrete PSMA-avid radiation fields on baseline PSMA-PET scan; all PSMA-avid lesions in radiation fields must be amenable to SBRT in judgment of treating radiation oncologist; there are no restrictions on site of lesion/radiation fields (e.g. bone, lymph node, prostate, visceral). Equivocal lesions/radiation fields on PSMA PET scan that are not definitive for metastasis will not count towards the limit of 5 radiation fields and will not undergo SBRT
	Surgically or medically castrated, with testosterone levels of < 50 ng/dL during screening; if the patient is medically castrated, continuous dosing with luteinizing hormone-releasing hormone (LHRH) analogue must have been initiated at least 4 weeks prior to randomization and must be continued throughout the study to maintain castrate levels of testosterone including post-treatment follow up period
	No prior systemic treatment initiated for the treatment of castration resistant prostate cancer, including abiraterone acetate, enzalutamide, apalutamide, darolutamide, other novel AR or CYP17 antagonist, or docetaxel
	Patients receiving bone loss prevention treatment with bone-modifying agents (e.g. denosumab, zoledronic acid) must be on stable doses for at least 4 weeks prior to randomization
	Patients who received a first generation anti-androgen (e.g., bicalutamide, flutamide, nilutamide) as most recent treatment must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after washout
	At least 4 weeks or 5 half-lives, whichever is shorter, must have elapsed from the use of any anti-cancer therapy, other than Luteinizing hormone-releasing hormone (LHRH) analog or first generation antiandrogen, prior to randomization
	At least 4 weeks must have elapsed from major surgery or radiation therapy prior to randomization
	Age > 18 years
	Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
	Resolution of all acute toxic effects of prior therapy or surgical procedure to grade 1 or baseline prior to randomization
	Serum aspartate transaminase (AST) ((serum glutamic oxaloacetic transaminase (SGOT])) and serum alanine transaminase (ALT) (( serum glutamic pyruvic transaminase (SGPT)) 2.5 x upper limit of normal (ULN)
	Total serum bilirubin 1.5 x ULN; in subjects with known or suspected Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, direct bilirubin is 1.5 x ULN
	Glomerular filtration rate 45 ml/min based on Cockcroft-Gault equation
	Absolute neutrophil count (ANC) 1500/microliter
	Platelets 75,000/microliter without transfusion and/or growth factors in the 3 months prior to randomization
	Hemoglobin 9.0 g/dL without transfusion and/or growth factors in the 3 months prior to randomization
	Serum albumin 3.0 g/dL
	Signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the trial prior to randomization
	Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets and long-term follow-up
	Agrees 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 agrees 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; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
Exclusion Criteria
	Presence of visceral lesions (e.g. lung, liver) detectable on baseline imaging or bone lesions requiring focal radiation treatment at the time of study entry
	History of seizure or condition that may pre-dispose to seizure (e.g., prior stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system (CNS) or meningeal disease which may require treatment with surgery or radiation therapy
	Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 1 week prior to randomization, except for medications known to lower seizure threshold which must be discontinued or substituted at least 4 weeks prior to randomization)
	Medications known to lower the seizure threshold
	Herbal (e.g., saw palmetto) and non-herbal (e.g., pomegranate) products that may decrease PSA levels
	Systemic (oral/intravenous (IV)/intramuscular (IM)) corticosteroids; patients on chronic stable dose of steroids at an equivalent dose of prednisone 10 mg daily may be permitted to enroll at the discretion of principal investigator
	Any other experimental treatment on another clinical trial
	Any of the following within 6 months prior to randomization: Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias
	Uncontrolled hypertension at study entry; patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by antihypertensive treatment
	Gastrointestinal disorder affecting absorption
	Secondary malignancy requiring active treatment except for non-melanoma skin cancer and superficial bladder cancer
	Any medical condition that would be a contra-indication to radiation therapy, such as inflammatory bowel disease
	Spinal cord compression or impending spinal cord compression
	Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

0/250

By sending a message, I agree that my data will be sent to a representative for the selected site and processed in accordance with this website's Privacy Policy (see link in footer).

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

glomerular filtration rate

adenocarcinoma of prostate

darolutamide

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Edit Delete

Added by •

•

Private

Edit Delete

Reply by • • Private

Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

Enter the passcode

The passcode will expire in None.

Apalutamide With or Without Stereotactic Body Radiation Therapy in Treating Participants With Castration-Resistant Prostate Cancer (PILLAR)