Clinical trial NCT04024254: A Study of Serum Folate Levels in Patients Treated With Olaparib
Official title: A Study of Serum Folate Levels in Patients Treated With Olaparib
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Ovarian Cancer
Breast Cancer
Folic Acid Deficiency
Keywords: ovarian cancer
breast cancer
olaparib
folic acid deficiency
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2019-07-18
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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. The primary goal of this study is to determine the frequency and timing of folate deficiency, and to learn more about whether giving folic acid supplements (vitamins) will help delay or avoid deficiency in these patients. Deficiency can cause doctors to reduce or stop treatment with olaparib. In this case, patients are not getting the best treatment for their cancer due to the unwanted side effect.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
* Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable).
* Participation in another clinical study with an investigational product administered in the last 1 month
* Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
* Patients with a known hypersensitivity to folic acid or any of the excipients of the product.
* Involvement in the planning and/or conduct of the study
* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
* Previous enrollment in the present study
* Breast feeding women

Primary outcomes:
measure: Frequency of Folate Deficiency
timeFrame: Up to approximately 2 years
measure: Timing of Folate Deficiency
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Complete Blood Count (CBC)
timeFrame: Up to approximately 2 years
measure: Serum folate
timeFrame: Up to approximately 2 years
measure: Number of required blood tranfusions
timeFrame: Up to approximately 2 years
measure: Number of olaparib dose interruptions
timeFrame: Up to approximately 2 years
measure: Number of olaparib dose reductions
timeFrame: Up to approximately 2 years
measure: Number of olaparib discontinuations
timeFrame: Up to approximately 2 years
measure: Response Rate to olaparib
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
References: