A Study of Serum Folate Levels in Patients Treated With Olaparib
Primary Purpose
Ovarian Cancer, Breast Cancer, Folic Acid Deficiency
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Folic Acid Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring ovarian cancer, breast cancer, olaparib, folic acid deficiency
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
Sites / Locations
- Rush University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Folic Acid
No Supplementation
Arm Description
Folic Acid supplement 1 mg by mouth daily
Outcomes
Primary Outcome Measures
Frequency of Folate Deficiency
The frequency of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
Timing of Folate Deficiency
The timing of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
Secondary Outcome Measures
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.
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.
Number of required blood tranfusions
The number of blood transfusions during olaparib treatment will be measured.
Number of olaparib dose interruptions
The number of interruptions in olaparib treatment will be measured.
Number of olaparib dose reductions
The number of reductions in olaparib treatment will be measured.
Number of olaparib discontinuations
The number of subjects who have their olaparib treatments discontinued will be measured.
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.
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.
Full Information
NCT ID
NCT04024254
First Posted
July 10, 2019
Last Updated
June 7, 2023
Sponsor
Rush University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04024254
Brief Title
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
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
July 21, 2020 (Actual)
Primary Completion Date
March 30, 2023 (Actual)
Study Completion Date
June 1, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Breast Cancer, Folic Acid Deficiency
Keywords
ovarian cancer, breast cancer, olaparib, folic acid deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Folic Acid
Arm Type
Experimental
Arm Description
Folic Acid supplement 1 mg by mouth daily
Arm Title
No Supplementation
Arm Type
No Intervention
Intervention Type
Drug
Intervention Name(s)
Folic Acid Tablet
Intervention Description
Folic Acid 1 mg by mouth daily
Primary Outcome Measure Information:
Title
Frequency of Folate Deficiency
Description
The frequency of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
Time Frame
Up to approximately 2 years
Title
Timing of Folate Deficiency
Description
The timing of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
Time Frame
Up to approximately 2 years
Secondary Outcome Measure Information:
Title
Complete Blood Count (CBC)
Description
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.
Time Frame
Up to approximately 2 years
Title
Serum folate
Description
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.
Time Frame
Up to approximately 2 years
Title
Number of required blood tranfusions
Description
The number of blood transfusions during olaparib treatment will be measured.
Time Frame
Up to approximately 2 years
Title
Number of olaparib dose interruptions
Description
The number of interruptions in olaparib treatment will be measured.
Time Frame
Up to approximately 2 years
Title
Number of olaparib dose reductions
Description
The number of reductions in olaparib treatment will be measured.
Time Frame
Up to approximately 2 years
Title
Number of olaparib discontinuations
Description
The number of subjects who have their olaparib treatments discontinued will be measured.
Time Frame
Up to approximately 2 years
Title
Response Rate to olaparib
Description
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.
Time Frame
Up to approximately 2 years
Title
Progression-free survival (PFS)
Description
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.
Time Frame
Up to approximately 2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
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A Study of Serum Folate Levels in Patients Treated With Olaparib
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