Clinical Trials /

Focal Radiation With Pulsed Systemic Therapy of Abiraterone, Androgen Deprivation Therapy (ADT), Lynparza Towards Castration Sensitive Oligometastatic Prostate Cancer (FAALCON)

NCT04748042

Description:

The purpose of this study is to assess the safety and effectiveness of radiation therapy with hormone therapy (ADT) and chemotherapy as an investigational study treatment for prostate cancer. This is a phase 2 study to deliver focal radiation with pulsed systemic therapy of Abiraterone, ADT and Lynparza (olaparib) in men with castration sensitive oligometastatic prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Focal Radiation With Pulsed Systemic Therapy of Abiraterone, Androgen Deprivation Therapy (ADT), Lynparza Towards Castration Sensitive Oligometastatic Prostate Cancer (FAALCON)
  • Official Title: Focal Radiation With Pulsed Systemic Therapy of Abiraterone, ADT, Lynparza Towards Castration Sensitive Oligometastatic Prostate Cancer (FAALCON): A Phase II, Single Arm, Single Institution Study

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2020.080
  • SECONDARY ID: HUM00187979
  • NCT ID: NCT04748042

Conditions

  • Prostate Cancer
  • Castrate Sensitive Prostate Cancer
  • Oligometastatic Disease

Interventions

DrugSynonymsArms
AbirateroneZytigaAbiraterone, ADT, Radiation and Olaparib
PrednisoneAbiraterone, ADT, Radiation and Olaparib
Androgen Deprivation Therapy (ADT)Abiraterone, ADT, Radiation and Olaparib
OlaparibLynparza, AZD2281Abiraterone, ADT, Radiation and Olaparib

Purpose

The purpose of this study is to assess the safety and effectiveness of radiation therapy with hormone therapy (ADT) and chemotherapy as an investigational study treatment for prostate cancer. This is a phase 2 study to deliver focal radiation with pulsed systemic therapy of Abiraterone, ADT and Lynparza (olaparib) in men with castration sensitive oligometastatic prostate cancer.

Trial Arms

NameTypeDescriptionInterventions
Abiraterone, ADT, Radiation and OlaparibExperimentalAbiraterone, ADT, radiation to all metastases and Olaparib.
  • Abiraterone
  • Prednisone
  • Androgen Deprivation Therapy (ADT)
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic or cytologic diagnosis of prostate adenocarcinoma (pure small cell or pure
             neuroendocrine prostate cancer are not allowed).

          -  Prior radical prostatectomy OR external beam radiation with curative intent (e.g. HiFU
             or partial gland therapies are not acceptable) delivered to prostate. Patients with
             prior radical prostatectomy with positive margins must have undergone salvage or
             adjuvant radiation.

          -  Have newly diagnosed oligometastatic prostate cancer based on molecular imaging (e.g.
             68Ga-PSMA PET/CT or Axumin, excludes FDG-PET). Oligometastatic prostate cancer is
             between 1 and ≤ 5 radiation treatment sites. A site can be up to 5 cm and contain
             multiple lesions.

          -  Newly diagnosed oligometastatic disease requires that no prior image guided radiation
             was given to sites outside of the prostate bed or pelvic lymph nodes that are
             typically treated in the salvage or adjuvant radiation setting.

          -  Patients must have a PSA >0.2 ng/mL (confirmed ≥4 weeks later with subsequent rise)
             for those who underwent radical prostatectomy. For those with prior curative
             radiotherapy, they must meet the Phoenix criteria for progression (nadir of PSA + 2
             ng/mL)

          -  Medically fit for radiotherapy

          -  All molecular positive disease is within an anatomic distribution that (in the view of
             the radiation oncologist) can be treated safely per standard radiation oncology
             principles

          -  Candidate for androgen deprivation therapy (e.g. leuprolide, goserelin, degarelix)
             abiraterone therapy (financial and medical) in view of medical oncology using package
             insert for guidance

          -  Patient must have normal organ and bone marrow function measured within 28 days prior
             to administration of study treatment as defined per protocol

          -  Androgen deprivation therapy with or without second generation androgen receptor
             inhibitors or abiraterone (when given to optimize focal therapies like surgery or
             radiation) in the curative setting are allowed as long as testosterone has recovered
             to above 150 ng/dL.

          -  Androgen deprivation therapy (with or without second generation androgen receptor
             inhibitors or abiraterone) for metastatic disease is allowed up to 4 weeks prior to
             registration. If previous ADT was used in curative setting, testosterone recovery must
             be documented (testosterone >150 ng/dL) OR >1 year elapsed from last administration of
             curative attempt ADT before recent ADT was resumed.

          -  ECOG ≤1

          -  Patients must use a condom during treatment and for 6 months after the last dose of
             olaparib or abiraterone when having sexual intercourse with a pregnant woman or with a
             woman of childbearing potential. Female partners of childbearing potential of patients
             on study should also use a highly effective form of contraception.

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  Prior orchiectomy

          -  Prior exposure to PARP inhibitors, docetaxel or cabazitaxel.

          -  Has a known additional malignancy within the past 3 years that has required treatment
             excluding superficial squamous skin cancer or carcinoma in situ of bladder or head and
             neck (those are permissible).

          -  Life expectancy ≤3 years in view of treating provider

          -  Presence of known parenchymal brain metastasis (imaging not required in absence of
             symptoms)

          -  Symptoms of cord compression requiring immediate radiation.

          -  Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with
             features suggestive of MDS/AML per primary provider

          -  Severe hepatic impairment (Child-Pugh Class C)

          -  Patients with known active hepatitis infection (e.g. hepatitis B, or C)

          -  Concurrent use of strong CYP3A inducers (e.g. phenytoin, carbamazepine, rifampin,
             rifabutin, rifapentine, phenobarbital, nevirapine, St. John's Wort) or moderate
             inducers (e.g bosentan, efavirenz or modafinil). The required washout period prior to
             starting olaparib is 5 weeks for phenobarbital or enzlautamide and 3 weeks for other
             agents. The washout requirement is measured from anticipated start of Olaparib, NOT
             from start of study.

          -  Concomitant use of known strong CYP3A inhibitors (e.g. intraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boveprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
             period prior to starting olaparib is 2 weeks. The washout requirement is measured from
             anticipated start of olaparib, NOT from start of study.

          -  Major surgery within 2 weeks of starting study treatment and patient must have
             recovered from any effects of any major surgery

          -  Clinically significant cardiovascular disease as evidenced by:

               -  myocardial infarction or arterial thrombotic events (e.g. stroke) in the past 6
                  months

               -  resting EKG indicating uncontrolled, potentially reversible cardiac candiation,
                  as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic
                  arrhythmia, QTc Fridericia prolongation >500 ms) or patients with congenital long
                  QT syndrome

               -  severe or unstable angina, uncontrolled atrial fibrillation (controlled atrial
                  fibrillation is allowed) or other (non-atrial fibrillation) cardiac arrhythmia
                  requiring therapy

               -  Active New York Heart Association Class II-IV heart failure

               -  if any prior history of CHF (regardless of New York Heart Association
                  assignment), a cardiac ejection fraction measurement (by echocardiography or
                  multigated acquisition scan) is required within 6 months and mush not be <50%.

          -  Planned or scheduled cardiac surgery or percutaneous coronary intervention procedure

          -  Prior revascularization procedure (coronary, carotid or peripheral artery stenosis)
             within the past 12 months

          -  History of uncontrolled pituitary or adrenal dysfunction

          -  Active infection or other medical condition that would make prednisone use
             contraindicated

          -  Any chronic medical condition requiring a systemic dose of corticosteroid >10 mg
             prednisone daily

          -  Prior allogeneic bone marrow transplant or double umbilical cord blood transplantation

          -  Participation in another clinical study with an investigational product or
             investigational medical devices within 1 month of registration

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             and Merck staff and/or staff at the University of Michigan).

          -  Judgment by the investigator that the patient should not participate in the study if
             the patient is unlikely to comply with study procedures, restrictions and
             requirements.

          -  Uncontrolled hypertension (systolic blood pressure ≥160 mmHg) of diastolic blood
             pressure ≥95 mmHg. Patients with documented white coat syndrome (with home blood
             pressure machine compared to office for calibration) are allowed if home blood
             pressure measured daily for a week meet eligibility

          -  Known hypersensitivity to olaparib, abiraterone, planned ADT agent (e.g. leuprolide,
             goserelin, degarelix), any of the excipients of any of these agents (olaparib,
             abiraterone, planned ADT agent) or drugs with a similar chemical structure to them or
             class to agents (olaparib, abiraterone or planned ADT)

          -  Immunocompromised patients

          -  Patients who are considered a poor medical risk due to a serious uncontrolled medical
             disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
             not discussed elsewhere include, but are not limited to uncontrolled seizure disorder,
             superior vena cava syndrome or any psychiatric disorder that prohibits informed
             consent

          -  Persistent toxicities (CTCAE Grade ≥2) caused by previous cancer therapy, excluding
             alopecia or sensory peripheral neuropathy

          -  Patients who are unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study medication
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients without treatment failure at 24 months
Time Frame:24 months after enrollment
Safety Issue:
Description:Treatment failure is defined as one of the following: New or progressive metastases on Computed Tomogrophy (CT)/Magnetic Resonance Imaging (MRI) per Response Evaluation Criteria In Solid Tumors (RECIST) New lesion(s) on bone scan without alternate explanations (e.g. trauma, arthritis) in distribution consistent with prostate cancer metastases, by provider assessment Clinical progression by provider assessment Prostate Specific Antigen (PSA) doubling time under 6 months with an absolute final PSA over 1.5 ng/mL

Secondary Outcome Measures

Measure:Percentage of patients with undetectable PSA, testosterone >150 ng/dL and without treatment failure.
Time Frame:Up to 36 months after enrollment
Safety Issue:
Description:The number of patients who achieve an undetectable PSA (PSA ≤ 0.2 ng/mL) AND have a testosterone >150 ng/dL will be divided by the number of patients treated in the study with a 95% confidence interval (CI). This will be analyzed at 12, 18, 24 and 36 months.
Measure:Rate of obtaining an optimal PSA (PSA ≤ 0.2 ng/mL)
Time Frame:Up to 36 months months after enrollment
Safety Issue:
Description:The number of patients who achieve an undetectable PSA (PSA ≤ 0.2 ng/mL) will be divided by the number of patients treated in the study with a 95% CI. This will be analyzed at 12, 18, 24 and 36 months.
Measure:Time to Androgen Deprivation Therapy (ADT) restart
Time Frame:Up to 36 months months after enrollment
Safety Issue:
Description:Time to ADT restart is defined as time from day 0 to restarting of gonadotropin-releasing hormone (GNRH) agonist or antagonist. The time to ADT restart may be determined by Kaplan-Meier methods.
Measure:Time to subsequent therapy (e.g. ADT, radiation)
Time Frame:Up to 36 months after enrollment
Safety Issue:
Description:Time to subsequent therapy (e.g. ADT or radiation) will be measured from day 0 to start of therapy and determined by Kaplan-Meier methods.
Measure:Frequency of adverse events grade 3 or higher and attributable to study treatment
Time Frame:Up to 36 months after enrollment
Safety Issue:
Description:Adverse events >= grade 3 and attributable to study treatment (possibly, probably, likely) will be reported by body system, severity and grade, and summarized by different levels of treatment exposure, per Common Terminology Criteria for Adverse Events (CTCAE) v.5.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Rogel Cancer Center

Trial Keywords

  • abiraterone
  • ADT
  • Lynparza
  • radiation

Last Updated

February 10, 2021