Targeting Resistant Prostate Cancer With ATR and PARP Inhibition (TRAP Trial)

NCT03787680 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: UMCC 2018.108HUM00152799
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the effectiveness (how well the drugs work), safety, and tolerability of the investigational drug combination of olaparib and AZD6738 for all patients with metastatic castration-resistant prostate cancer.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Rate of Response (Complete Response [CR] or Partial Response [PR]) in DNA Repair Proficient (DRPro) Patients

  Evaluated per radiographic response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or by Prostate Specific Antigen (PSA) (≥50% decline).

  Up to 30 days after study completion (an average of 1 year)

Secondary Outcomes (13)

• Rate of Response (Complete Response [CR] or Partial Response [PR]) in DNA Repair Deficient (DRDef) Patients

  Up to 30 days after study completion (an average of 1 year for study completion)

• Progression-free Survival (PFS) in DRPro Patients

  Up to 30 days after study completion (an average of 1 year for study completion)

• Progression-free Survival (PFS) in DRDef Patients

  Up to 30 days after study completion (an average of 1 year for study completion)

• Radiographic Response Rate in DRPro Patients

  Up to 30 days after study completion (an average of 1 year for study completion)

• Radiographic Response Rate in DRDef Patients

  Up to 30 days after study completion (an average of 1 year for study completion)

Study Arms (2)

Cohort 1 (DRPro)

EXPERIMENTAL

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair proficient (DRPro).

Drug: Olaparib; Drug: AZD6738

Cohort 2 (DRDef)

EXPERIMENTAL

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair deficient (DRDef).

Drug: Olaparib; Drug: AZD6738

Interventions

Olaparib DRUG

300 mg by mouth twice a day for days 1-28 of a 28-day cycle.

Also known as: AZD2281, ceralasertib

Cohort 1 (DRPro); Cohort 2 (DRDef)

AZD6738 DRUG

160 mg by mouth daily for days 1-7 of a 28-day cycle.

Cohort 1 (DRPro); Cohort 2 (DRDef)

Eligibility Criteria

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

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Male ages 18 years and older at time of signing the informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 42 days prior to registration
• Histologic or cytologic proof of prostate adenocarcinoma (excluding small-cell or neuroendocrine pathologies)
• Metastatic prostate cancer on CT, MRI or Bone scan
• Must have disease progression (while testosterone level is under 50 ng/dl) on prior therapy prior to study entry defined as one (or more) of the following:
• PSA progression defined as continuously rising PSA values measured a minimum of 1 week apart with a minimal starting value of 1.0 ng/mL
• Progression of bidimensionally measurable soft tissue or nodal metastasis by CT or MRI based on RECIST, v1.1
• Prior treatment with at least one of the following:
• One line of therapy in mCRPC
• Second generation anti-androgen (e.g. abiraterone, enzalutamide or apalutamide) within the hormone-sensitive phase of disease AND progression occurs while on therapy
• Patients must be withdrawn from prior therapy for ≥3 weeks (patients may remain on prior prednisone up to 10 mg total daily exposure at provider's discretion) at planned time of treatment start.
• Agree to undergo a biopsy of at least one metastatic site (if feasible) to determine DNA repair status, unless prior metastatic tissue underwent next-generation sequencing in a CLIA certified lab or known germline loss of BRCA1, BRCA2 or ATM. If no site is reachable, or first biopsy insufficient/unsuccessful, circulating tumor DNA may be obtained.
• Treated with continuous androgen deprivation therapy (either surgical castration or LHRH agonist/antagonist) with documented castrate level of serum testosterone (\<50 ng/dL). A stable dose of bisphosphonate or denosumab for bone metastases should be continued as long as started at least 5 days prior to C1D1 planned start day.
• At the time of planned treatment start (C1D1), at least 21 or more days will have elapsed from palliative radiation (with the exception of radiation to \>30% of bone marrow or with a wide field of radiation, this requires 28 or more days).

You may not qualify if:

• A diagnosis of ataxia telangiectasia
• Prior treatment with a PARP inhibitor (e.g. olaparib, veliparib, niraparib, rucaparib), AZD6738 or other DNA-damage response agents (e.g. cisplatin or carboplatin)
• Cytotoxic chemotherapy, first- or second-generation antiandrogen or CYP17 inhibitors are not permitted within 21 days or 5 half-lives of registration (whichever is longest) of planned treatment start. For clarity, enzalutamide requires 5 weeks washout.
• Major surgery \< 2 weeks prior to enrolment; patients must have recovered from any effects of major surgery
• Persistent toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, besides Grade 2 alopecia and Grade 2 neuropathy (these are allowed).
• Patients with current or prior MDS/AML or with features suggestive of MDS/AML
• Any other malignancy which has been active or treated within the past 3 years, with the exception of non-melanomatous skin cancer, or Ta bladder cancer
• Patients with active brain metastases are excluded because of unknown penetration into the CNS. A confirmatory scan for asymptomatic patients is not required. Patients with a history of treated central nervous system (CNS) metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 3 weeks between completion of radiotherapy and registration and recovery from significant (Grade ≥ 3) acute toxicity with no ongoing requirement for \>10 mg of prednisone per day or an equivalent dose of other corticosteroid. If a patient must remain on steroids, they must have started the steady dose at least 28 days prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days prior to study treatment.
• Any of the following cardiac disease currently or within the last 6 months:
• Unstable angina pectoris
• Congestive heart failure (by New York Heart Association ≥ Class 2) or known reduced LVEF \< 55%
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication (e.g. complete left bundle branch block or third-degree heart block)
• Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
• Uncontrolled hypertension (Grade 2 or above) requiring urgent (for example, adjusting medications within 24 hours) clinical intervention

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (3)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; ceralasertib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Zachery Reichert, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: December 26, 2018
• Study Start: October 31, 2019
• Primary Completion: January 26, 2023
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 23, 2026
• Results First Posted: August 12, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)