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出境医 / 临床实验 / A Study of Serum Folate Levels in Patients Treated With Olaparib

A Study of Serum Folate Levels in Patients Treated With Olaparib

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Breast Cancer Folic Acid Deficiency Drug: Folic Acid Tablet Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Serum Folate Levels in Patients Treated With Olaparib
Actual Study Start Date : July 21, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : March 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Folic Acid
Folic Acid supplement 1 mg by mouth daily
Drug: Folic Acid Tablet
Folic Acid 1 mg by mouth daily

No Intervention: No Supplementation
Outcome Measures
Primary Outcome Measures :
  1. Frequency of Folate Deficiency [ Time Frame: Up to approximately 2 years ]
    The frequency of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.

  2. Timing of Folate Deficiency [ Time Frame: Up to approximately 2 years ]
    The timing of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.


Secondary Outcome Measures :
  1. Complete Blood Count (CBC) [ Time Frame: Up to approximately 2 years ]
    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.

  2. Serum folate [ Time Frame: Up to approximately 2 years ]
    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.

  3. Number of required blood tranfusions [ Time Frame: Up to approximately 2 years ]
    The number of blood transfusions during olaparib treatment will be measured.

  4. Number of olaparib dose interruptions [ Time Frame: Up to approximately 2 years ]
    The number of interruptions in olaparib treatment will be measured.

  5. Number of olaparib dose reductions [ Time Frame: Up to approximately 2 years ]
    The number of reductions in olaparib treatment will be measured.

  6. Number of olaparib discontinuations [ Time Frame: Up to approximately 2 years ]
    The number of subjects who have their olaparib treatments discontinued will be measured.

  7. Response Rate to olaparib [ Time Frame: Up to approximately 2 years ]
    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.

  8. Progression-free survival (PFS) [ Time Frame: Up to approximately 2 years ]
    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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Lois Winkelman, RN 312-942-2417 Lois_Winkelman@rush.edu

Locations
Layout table for location information
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Lois Winkelman, RN    312-942-2417      
Sponsors and Collaborators
Rush University Medical Center
Tracking Information
First Submitted Date  ICMJE July 10, 2019
First Posted Date  ICMJE July 18, 2019
Last Update Posted Date July 24, 2020
Actual Study Start Date  ICMJE July 21, 2020
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Frequency of Folate Deficiency [ Time Frame: Up to approximately 2 years ]
    The frequency of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
  • Timing of Folate Deficiency [ Time Frame: Up to approximately 2 years ]
    The timing of folate deficiency in patients with ovarian and breast cancers who are treated with olaparib will be measured.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Complete Blood Count (CBC) [ Time Frame: Up to approximately 2 years ]
    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 [ Time Frame: Up to approximately 2 years ]
    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 [ Time Frame: Up to approximately 2 years ]
    The number of blood transfusions during olaparib treatment will be measured.
  • Number of olaparib dose interruptions [ Time Frame: Up to approximately 2 years ]
    The number of interruptions in olaparib treatment will be measured.
  • Number of olaparib dose reductions [ Time Frame: Up to approximately 2 years ]
    The number of reductions in olaparib treatment will be measured.
  • Number of olaparib discontinuations [ Time Frame: Up to approximately 2 years ]
    The number of subjects who have their olaparib treatments discontinued will be measured.
  • Response Rate to olaparib [ Time Frame: Up to approximately 2 years ]
    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) [ Time Frame: Up to approximately 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Serum Folate Levels in Patients Treated With Olaparib
Official Title  ICMJE A Study of Serum Folate Levels in Patients Treated With Olaparib
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ovarian Cancer
  • Breast Cancer
  • Folic Acid Deficiency
Intervention  ICMJE Drug: Folic Acid Tablet
Folic Acid 1 mg by mouth daily
Study Arms  ICMJE
  • Experimental: Folic Acid
    Folic Acid supplement 1 mg by mouth daily
    Intervention: Drug: Folic Acid Tablet
  • No Intervention: No Supplementation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2019)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lois Winkelman, RN 312-942-2417 Lois_Winkelman@rush.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04024254
Other Study ID Numbers  ICMJE 18070604
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lydia Usha, Rush University Medical Center
Study Sponsor  ICMJE Rush University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Rush University Medical Center
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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