Efficacy of Rotations Between Abiraterone Acetate and Apalutamide in mCRPC Patients

NCT03173859 | Withdrawn Phase 2

• 2 other identifiers: 70/3/140732017-000443-41
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A randomized phase II study comparing the sequential use of abiraterone followed after progression by apalutamide with alternating cycles of abiraterone and apalutamide

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

prostate cancer, abiraterone, apalutamide

Outcome Measures

Primary Outcomes (1)

• Radiographic progression-free survival

  time until radiographic progression as assessed by PCWG2 criteria

  Estimated up to 24 months

Secondary Outcomes (4)

• Overall survival

  estimated up to 36 months

• Time to cytotoxic therapy initiation

  Estimated up to 24 months

• Time until PSA progression

  Estimated up to 24 months

• Incidence, nature and severity of AEs

  Estimated up to 24 months

Other Outcomes (3)

• Patient reported outcomes assessed using the FACT-P and EQ-5D-5L questionnaires

  Estimated up to 24 months

• Number of Circulating Tumor Cells (CTCs) and ARv7 analysis in CTCs from peripheral blood at baseline evaluation, first and second disease progression in Arm 2 and disease progression in Arm 1 (PD1).

  Estimated up to 24 months

• Patient reported outcomes assessed using the EQ-5D-5L questionnaires

  Estimated up to 24 months

Study Arms (2)

Rotational

EXPERIMENTAL

Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 for 3 cycles, followed by apalutamide 240mg qD orally for 3 cycles. The duration of each cycle is 28 days

Drug: Abiraterone; Drug: Apalutamide

Sequential

ACTIVE COMPARATOR

Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 until disease progression, followed by apalutamide 240mg qD orally until second disease progression.

Drug: Abiraterone; Drug: Apalutamide

Interventions

Abiraterone DRUG

Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally

Also known as: Zytiga

Rotational; Sequential

Apalutamide DRUG

apalutamide 240mg qD orally

Rotational; Sequential

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Age \>18 years Histologically confirmed metastatic or advanced prostate cancer adenocarcinoma that has received no treatment for the castration resistant disease and has progressed during treatment with complete androgen blockade (luteinizing hormone releasing hormone agonist or antagonist and an antiandrogen eg. Bicalutamide).
• Availability of a representative formalin-fixed, paraffin-embedded tumor specimen (FFPE) that enabled definitive diagnosis of prostate cancer.
• Two rising PSA levels \>2ng/ml measured 1 week apart during or following the most recent prior therapy for prostate cancer (PCWG2 criteria) or radiographic evidence of disease progression in bone with or without biochemical disease progression on the basis of the PSA value.
• Ongoing androgen deprivation, with serum testosterone \<50ng/dl ECOG performance status 0-1 at screening Adequate hematologic and organ function within 14 days before the first study treatment (hematologic parameters must be assessed \>14 days after a prior transfusion, if any) as defined by
• Hemoglobin \>9g/dl
• Neutrophils \>1500/μL
• Platelet count \>100000/μL
• Total bilirubin \<1,5xULN with the following exception:
• o Patients with known Gilbert syndrome who have serum bilirubin\<3xULN
• AST and ALT\<2,5xULN with the following exception
• o Patients with bone-only metastasis may have AST\<5xULN, provided that ALT \<2,5xULN and total bilirubin \<1,5xULN
• Serum albumin \>3g/dl
• Serum potassium ≥3.5mmol/L
• Serum creatinine \<1,5xULN or creatinine clearance of \>50ml/min based on Cockcroft-Gault equation
• Agreement by patient and/or partner to use an effective form of contraception including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants or true abstinence and to continue its use for the duration of the study and for 6 months after the last dose of study treatment.

You may not qualify if:

• Small cell or neuroendocrine prostate carcinoma Inability or unwillingness to swallow pills Malabsorption syndrome or other condition that would interfere with enteral absorption Congenital long QT syndrome or QTc\>480msec NYHA Class II to IV heart failure or LVEF \<50% or ventricular arrhythmia requiring medication Previous therapy for prostate cancer with CYP17 inhibitors including ketoconazole or investigational agents (VMT-VT-464, Orteronel etc) or novel antiandrogens (enzalutamide of OMD-208) for more than 7 days Presence of visceral metastasis History of another invasive cancer within 3 years from screening, with the exception of fully treated cancers with a remote probability of recurrence Duration of previous Androgen Deprivation Therapy \<12months Active infection requiring IV antibiotics
• Clinically significant cardiovascular disease including the following:
• unstable angina,
• myocardial infarction within 6 months from screening, or
• cerebrovascular accident within 6 months from screening Major surgical procedure within 4 weeks prior to initiation of study treatment Treatment with an investigational agent within 4 weeks prior to initiation of study treatment Unresolved, clinical significant toxicity from prior treatment Hypersensitivity reaction to the active pharmaceutical ingredient or any of the tablet components Any medical condition that restrain the patient to comply with study and follow-up procedures Inability to comply with study and follow up procedures

Sponsors & Collaborators

• University of Athens: lead

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms

Interventions

abiraterone; Abiraterone Acetate; 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)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 28, 2017
• First Posted: June 2, 2017
• Study Start: January 1, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: November 18, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share