A Study of Serum Folate Levels in Patients Treated With Olaparib

Study Overview
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Brief Summary
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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.

Official Title
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A Study of Serum Folate Levels in Patients Treated With Olaparib

Conditions
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Ovarian Cancer, Breast Cancer, Folic Acid Deficiency

Intervention / Treatment
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* Drug: Folic Acid Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folic Acid<br>Folic Acid supplement 1 mg by mouth daily | Drug: Folic Acid Tablet<br>* Folic Acid 1 mg by mouth daily<br>|
| No Intervention: No Supplementation<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Folate Deficiency | The frequency of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured. | Up to approximately 2 years | 
| Timing of Folate Deficiency | The timing of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Blood Count (CBC) | To evaluate the effect of folic acid supplementation on hemoglobin level, CBC will be measured every 2 weeks for the first 3 months, and then monthly thereafter for duration of olaparib therapy. Hematological toxicity will be assessed by utilizing CTC Version 4.0. | Up to approximately 2 years | 
| Serum folate | To evaluate the effect of folic acid supplementation on serum folate levels, serum folate will be measured every 2 weeks for the first 3 months, and then monthly thereafter for duration of olaparib therapy. | Up to approximately 2 years | 
| Number of required blood tranfusions | The number of blood transfusions during olaparib treatment will be measured. | Up to approximately 2 years | 
| Number of olaparib dose interruptions | The number of interruptions in olaparib treatment will be measured. | Up to approximately 2 years | 
| Number of olaparib dose reductions | The number of reductions in olaparib treatment will be measured. | Up to approximately 2 years | 
| Number of olaparib discontinuations | The number of subjects who have their olaparib treatments discontinued will be measured. | Up to approximately 2 years | 
| Response Rate to olaparib | The response rate will be assessed by treating physicians. The data on the response rate will be collected and correlated with hematologic toxicity, serum folate level, and folic acid supplementation. | Up to approximately 2 years | 
| Progression-free survival (PFS) | Investigators will compare progression free survival in Lynparza- treated patient with folate deficiency who were subsequently treated with folic acid to those who did not develop folate deficiency and did not require supplementation. | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, breast cancer, olaparib, folic acid deficiency