Trial Title:
Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer
NCT ID:
NCT05501548
Condition:
Prostate Cancer
Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Ascorbic Acid
Olaparib
Conditions: Keywords:
olaparib
ascorbic acid
PARP
PARP-inhibitor
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Olaparib 300mg by mouth twice daily
Arm group label:
Olaparib and Vitamin C
Other name:
Lynparza
Other name:
AZD2281
Other name:
KU-0059436
Intervention type:
Dietary Supplement
Intervention name:
Vitamin C
Description:
Ascorbic acid 1g/kg administered intravenously twice weekly
Arm group label:
Olaparib and Vitamin C
Other name:
Ascorbic acid
Other name:
L-ascorbic acid
Other name:
Ascor
Other name:
A11GA01
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). 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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).
- 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.
Exclusion Criteria:
- 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
- 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-inter
actions-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.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sibley Memorial Hospital
Address:
City:
Washington
Zip:
20016
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jan Powers, MSN
Phone:
202-660-6324
Email:
jpower22@jhmi.edu
Investigator:
Last name:
Channing Paller, MD
Email:
Principal Investigator
Facility:
Name:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kathy Schultz, RN
Phone:
410-614-9482
Email:
kschult3@jhmi.edu
Investigator:
Last name:
Channing Paller, MD
Email:
Principal Investigator
Start date:
June 30, 2023
Completion date:
March 2028
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
McGuff Pharmaceuticals, Inc.
Agency class:
Industry
Collaborator:
Agency:
The Marcus Foundation
Agency class:
Other
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05501548
