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Prostate CancerPhase 2NCT05501548

Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer

A Phase 2 study testing Olaparib and Vitamin C in people with Prostate Cancer and Castration-resistant Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 is a study to evaluate the safety and clinical activity of the combination of olaparib and high-dose IV ascorbate, as second or later line of therapy, in castration resistant prostate cancer patients with no known DNA repair gene mutations (DDRm). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Olaparib and Vitamin C
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
2 sitesUnited States
Study dates
30 Jun 2023to 14 Oct 2024
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

  • Have metastatic castration-resistant prostate cancer (prostate cancer progressing by PSA (rise by 25% on prior therapy) or imaging despite castrate levels of testosterone [<50 ng/dL] using standard measures of progression defined by Prostate Cancer Working Group3)
  • Have a minimum PSA of 1 ng/mL
  • Have a pathological diagnosis of prostate carcinoma
  • Patients should continue receiving continuous hormonal ablation with surgical or medical castration with baseline testosterone <50ng/dL
  • Patients may be receiving bone-targeted agents
  • May have received multiple lines of therapy including radium 223, sipuleucel T, and up to 2 lines of chemotherapy (One of 2 lines may be for hormone sensitive metastatic prostate cancer or both can be for castration resistant).
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  • Age >= 18
  • Have ECOG performance status 0-1 (Appendix A)
  • Be able to take oral medication and willing to consider a port for ease of administration of ascorbate
  • Must have progressed on one systemic line of treatment (can include LHRH agonist/antagonist or orchiectomy and one additional line of therapy (abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, etc))
  • Have normal organ and marrow function measured within 28 days prior to administration of study treatment as defined below:
  • Absolute neutrophil count >1.5 x 109/L
  • Platelets ≥ 100,000/mm³
  • Hemoglobin ≥ 9g/dL with no blood transfusion in the past 28 days
  • Total bilirubin ≤ 1.5 ULN
  • AST (SGOT)/ALT(SGPT) ≤ 2.5 x ULN (≤5x ULN if with known liver metastases provided bilirubin is normal
  • Creatinine ≤ 1.6 x ULN (for patients with ≥1.6 x ULN, calculated or measured creatinine clearance must be ≥ 60 mL/minute (Cockcroft-Gault)
  • Men of reproductive potential and those who are surgically sterilized (i.e. post- vasectomy) must agree to practice effective barrier contraception that has an expected failure rate of <1% during and for 6 months after discontinuation of study treatment. Female partners should also use a highly effective form of contraception ([see Appendix C for acceptable methods]) if they are of childbearing potential.
  • If condoms are used as a barrier contraceptive, a spermicidal agent should be added to ensure that pregnancy does not occur
  • Have the ability to understand, and have given written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Who cannot join

  • Have a known DNA repair mutation (minimum list of genes that must be mutation negative for inclusion: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD45L). In addition, patients who have not completed germline and somatic testing to rule out such a mutation are ineligible until they have completed testing. If tissue or liquid ctDNA sequencing was not previously done, testing using the Foundation One liquid biopsy test or an equivalent FDA-approved test is acceptable as standard of care.
  • DNA repair mutation variant of unknown significance (VUS) allowed
  • Have had known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks 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.
  • No prior olaparib, rucaparib, or other PARP inhibitor
  • Have had major surgery within 2 weeks of dosing of investigational agent
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  • Have had palliative radiation or another biological cancer therapy within 2 weeks prior to the first dose of study drug (2 week wash out required)
  • Patients receiving any systemic chemotherapy or radiotherapy within 3 weeks prior to study treatment
  • Have received other investigational drugs within 14 days prior to enrollment.
  • Is expected to require chemotherapy or radiation for pain palliation in the next 12 weeks.
  • Have used or plan concomitant use of the following medications in the past 6 months prior to enrollment: 5-alpha reductase inhibitors unless subject has been taking stable dose of medication for prior 6 months
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks. See the following link for a complete list of known CYP3A inhibitors: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents. See the following link for a complete list of known CYP3A inhibitors:https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
  • Have moderate or severe cardiovascular disease:
  • Has the presence of cardiac disease, including a myocardial infarction within six months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
  • Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTc prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
  • Have uncontrolled intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Other malignancy unless curatively treated with no evidence of disease for >5 years except adequately treated non-melanoma skin cancer
  • Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
  • Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Patients with known active hepatitis (i.e. Hepatitis B or C)
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21287

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

This is a study to evaluate the safety and clinical activity of the combination of olaparib and high-dose IV ascorbate, as second or later line of therapy, in castration resistant prostate cancer patients with no known DNA repair gene mutations (DDRm). In brief, the primary endpoint is PSA50 response , defined by a 50% reduction in PSA from baseline . The secondary endpoints are assessing the PSA doubling time, radiographic and PSA PFS, safety and tolerability as defined by the incidence of grade 3 to 5 toxicities, and measuring overall survival.

Being tested
Olaparib, Vitamin C
Keywords
olaparib, ascorbic acid, PARP, PARP-inhibitor
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • OlaparibDrug

    Also called Lynparza, AZD2281, KU-0059436

    Olaparib 300mg by mouth twice daily

  • Vitamin CDietary supplement

    Also called Ascorbic acid, L-ascorbic acid, Ascor, A11GA01

    Ascorbic acid 1g/kg administered intravenously twice weekly

Study groups in NCT05501548
Study groupRoleWhat they receive
Olaparib and Vitamin CExperimentalOlaparib will be administered at 300 mg by mouth, twice daily; ascorbate will be administered at 1 g/kg IV twice weekly at least 24 hours apart, until objective disease progression or unacceptable toxicities or patient withdrawal for other reasons.
Receives: Drug: Olaparib; Dietary Supplement: Vitamin C

What is being measured

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

  1. PSA50 Response

    Number of participants with metastatic castration resistance prostate cancer (mCRPC) who experience a 50% reduction in prostate specific antigen (PSA50) from baseline. PSA50 response will be defined as a decrease in the PSA to 50% less than the baseline PSA upon enrollment in the trial. The decrease must be confirmed by a second measurement at least 4 weeks apart. PSA values will be measured monthly during the trial.

    Measured: up to 5 years

Secondary outcomes (5)

  1. Safety and Tolerability of Olaparib in Combination With IV Ascorbic Acid in Patients With mCRPC

    Number of participants experiencing treatment-related adverse events as defined by NCI CTCAE v5.0.

    Measured: up to 1 year 4 months

  2. PSA Doubling Time in Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid

    Median number of months to PSA doubling from the initiation of therapy until the PSA has increased to 200% of baseline value, and confirmed with another measurement at least 4 weeks later, or death. The date of PSA doubling will be the first value recorded (not the confirmatory value).

    Measured: up to 5 years

  3. Radiographic Progression Free Survival (rPFS) of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid

    Number of months from initiation of therapy to date of first radiographic progression, death from any cause, or last patient evaluation. Radiographic progression will be defined as soft tissue disease progression by modified RECIST criteria 1.1 (baseline LN size must be >1.0 cm to be considered target or evaluable lesion) or by development of two or more new bone lesions not consistent with tumor flair for prostate cancer working group 3.

    Measured: up to 5 years

  4. PSA Progression Free Survival (PSA PFS) of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid

    Number of months to first PSA failure (two consecutive increases in PSA of 50% and >=5ng/mL above nadir) or death

    Measured: up to 5 years

  5. Overall Survival of Patients With mCRPC Receiving Olaparib in Combination With IV Ascorbic Acid

    Number of months from initiation of therapy to death due to any cause

    Measured: up to 5 years

Timeline

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

  1. First posted15 Aug 2022
  2. Study start30 Jun 2023
  3. Primary completion14 Oct 2024
  4. Study completion14 Oct 2024

Why it stopped: The study was terminated by the IRB due to low accrual,

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
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05501548
Sponsor's protocol ID
J21127
Other IDs
IRB00292465, ESR 19-20448
Status last verified
Jan 2025
First submitted
11 Aug 2022
Last updated
29 Jan 2025
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 Olaparib and Vitamin C in people with Prostate Cancer and Castration-resistant Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 20 inclusion and 25 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 29 Jan 2025. 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 29 Jan 2025). 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?

PSA50 Response (time frame: up to 5 years). 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 NCT05501548.

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 29 Jan 2025.

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