A Study of Serum Folate Levels in Patients Treated With Olaparib

NCT04024254 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 18070604
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study investigating folate deficiency (lack of folic acid in the blood) in patients who take the drug olaparib to treat their advanced ovarian or breast cancer.

Conditions

Ovarian Cancer; Breast Cancer; Folic Acid Deficiency

Keywords

ovarian cancer; breast cancer; olaparib; folic acid deficiency

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Have Developed Folate Deficiency (Serum Folate Level < 7 ng/ml) on Olaparib

  The number of patients with ovarian and breast cancers who were treated with olaparib and developed folate deficiency was counted.

  Serum folate levels were measured in each enrolled subject: at baseline, then every 2 weeks X 3 months, then monthly X 9 months. Accrual occurred over a 2-year period.

• Timing of Folate Deficiency Development

  The number of weeks between the beginning of olaparib treatment and the development of folate deficiency

  From the beginning of olaparib treatment until the development of folate deficiency

Secondary Outcomes (6)

• The Number of Participants Who Developed Decreased Hemoglobin by ≥ 1 g/dl Relative to Baseline

  Hemoglobin levels were measured in each enrolled subject: at baseline, then every 2 weeks X 3 months, then monthly X 9 months. Accrual occurred over a 2-year period.

• Serum Folate

  Serum folate levels were measured in each enrolled subject: at baseline, then every 2 weeks X 3 months, then monthly X 9 months. Accrual occurred over a 2-year period.

• Number of Participants Requiring Blood Transfusions

  Over 12 months while on olaparib therapy.

• Number of Participants Requiring Olaparib Dose Interruptions

  Over 12 months while on olaparib therapy.

• Number of Participants Requiring Olaparib Dose Reductions for Any Reason

  Over 12 months while on olaparib therapy.

Study Arms (2)

Folic Acid supplementation

EXPERIMENTAL

Folic Acid supplement 1 mg by mouth daily

Drug: Folic Acid Tablet

No Folic Acid Supplementation

NO INTERVENTION

No Folic Acid supplementation.

Interventions

Folic Acid Tablet DRUG

Folic Acid 1 mg by mouth daily

Folic Acid supplementation

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide signed informed consent
• Female, post-menopausal, ≥18 years of age inclusive, at the time of signing the consent form
• Individuals who have ovarian cancer or breast cancer who are recommended to start olaparib
• Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
• Haemoglobin ≥ 9 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
• Patients must have creatinine clearance estimated of ≥51 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1).
• Patients must have a life expectancy ≥ 16 weeks.
• At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT and is suitable for repeated assessment.

You may not qualify if:

• Patients with folic acid deficiency, defined as folate \<7 ng/mL, or those taking folic acid supplementation within 30 days of olaparib initiation.
• Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localised triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
• Patients with known active hepatitis (i.e. Hepatitis B or C).
• Any previous treatment with PARP inhibitor, including Olaparib.
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Breast Neoplasms; Folic Acid Deficiency

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

1. Low accrual at a single center led to a small sample size. 2. Close serum folate monitoring with early intervention for folate deficiency could have prevented more severe anemia, blood transfusions, and olaparib dose reductions. 3. Subjects were not blinded to results and may have altered their behavior. They were encouraged to hold folate-containing multivitamins but were not required to. 4. Olaparib-induced nausea and poor oral intake could have contributed to folate deficiency.

Results Point of Contact

• Title: Dr Lydia Usha
• Organization: Rush University Medical Center

Lydia_Usha@rush.edu

312-942-5904

Study Officials

• Lydia Usha, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 18, 2019
• Study Start: July 21, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 4, 2026
• Results First Posted: November 21, 2025

Record last verified: 2026-02

Locations

US (1)