This study is currently recruiting participants.
Number
19-C-0023
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
PARP Inhibitor; BRCA Loss; DNA-Repair Defects; FoundationOne
Recruitment Keyword(s)
None
Condition(s)
Urothelial Carcinoma
Investigational Drug(s)
Olaparib
Investigational Device(s)
Intervention(s)
Drug: Olaparib
Supporting Site
National Cancer Institute
People with bladder cancer are usually treated with single-drug taxanes. Researchers want to test a new treatment with the drug Olaparib. The drug is a targeted cancer therapy that stops cancer cells from fixing themselves so they do not live. It is approved for other cancers but not bladder cancer.
Objectives:
To test the good and bad side effects of Olaparib. To learn how many people with bladder cancer have certain genetic changes and markers.
Eligibility:
Adults at least 18 years old with bladder cancer
Design:
Participants will be screened with a review of medical records and tumor sample. They will also have blood, urine, and heart tests. Women will have a pregnancy test.
Participants will take the study drug in 4-week cycles. They may have up to 27 cycles.
Participants will take the drug by mouth 1 time every day. They will keep a diary of when they take their pills.
Participants will have a study visit every 4 weeks for blood and urine tests. They will review their study drug diary. They will have scans at some visits.
Participants will have blood taken for genetic testing 3 times over 12 weeks.
Participants can agree to have their samples and data saved for future research. They may give a saliva sample.
Participants may agree to have tumor tissue collected after starting the study drug. A needle is inserted in the tumor 3-6 times to take samples.
Participants will have a phone interview every 3 months for the first year after stopping the study drug. Then they will have 1 each year after that.
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INCLUSION CRITERIA: -Patients must have a histologically confirmed diagnosis non prostate GU cancer. -Patients with the presence of cancer-associated genetic mutations in one or more pathogenic or likely pathogenic gene alterations tested in the FoundationOne FoundationOne(Registered Trademark)CDx (F1CDx) panel will be enrolled in Cohorts 1 or 2 as follows: --Cohort 1: BRCA1, BRCA2, ATM, BAP1, PALB2, and BRIP1, or tumor mutational burden (TMB) where 10 or greater mutations/megabase. --Cohort 2: ABL1 FANCE POLD1 ATR FANCG POLE ATRX FANCL RAD51 BARD1 IKBKE SMARCB1 BRD4 MEN1 STK11 CCND1 MLH1 TP53 CHEK1 MSH2 CHEK2 MSH6 DOT1L MUTYH FANCA NPM1 FANCC PMS2 -Patients with benign or variants of unknown significance as determined by FoundationOne FoundationOne (Registered Trademark) CDx (F1CDx) panel and Genetics Review Panel review will be enrolled in Cohort 3 to be followed for survival. -Foundation One mutation analysis results performed prior to enrollment on this study may be accepted for eligibility review and in the event that a patient cannot undergo a biopsy and tumor is not available, Foundation Medicine liquid biopsy may be performed. -Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm (greater than or equal to 2 cm) by chest x-ray or as greater than or equal to 10 mm (greater than or equal to 1 cm) with CT scan, MRI, or calipers by clinical exam. -Evidence of disease progression as defined by RECIST (version 1.1) during treatment or after the most recent dose of therapy with at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor (atezolizumab, pembrolizumab, nivolumab, avelumab or durvalumab) (2-week washout from chemotherapy and 4-weeks washout from monoclonal antibodies is required). -Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of olaparib in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. -ECOG performance status less than or equal to 1 (or Karnofsky greater than or equal to 70%). -Patients must have normal organ and marrow function as defined below: --leukocytes greater than or equal to 3,000/mcL --absolute neutrophil count greater than or equal to 1,500/mcL --platelets greater than or equal to 100,000/mcL --total bilirubin less than or equal to 1.5 x ULN (for subjects with documented Gilbert s disease total bilirubin less than or equal to 3.0 mg/dL) --AST(SGOT)/ALT(SGPT) less than or equal to 2.5 x institutional upper limit of normal (for subjects with liver metastasis AST/ALT less than or equal to 5x ULN) --creatinine clearance greater than or equal to 50 mL/min/1.73 m^2 --hemoglobin greater than or equal to 10 g/dL; transfusions are allowed --PT/INR and aPTT Within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on direct oral anticoagulant (DOA) -Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib. -Pre-clinical data indicate that olaparib adversely affects embryofetal survival and development. Therefore, women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least six (6) months after the last dose of olaparib. Male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib. Note: Olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib. -Ability to understand and the willingness to sign a written informed consent document or patients with Impaired Decision Making Capacity (IDMC) if they are represented by a Legally Authorized Representative (LAR). -Patients must provide archival tumor sample for mutation analysis or be willing to undergo screening biopsy. In the event that a patient cannot undergo biopsy and tumor is not available, Foundation Medicine liquid biopsy will be performed. -Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment at screening. Note: This will also need to be confirmed within 3 days prior to treatment on day 1. Postmenopausal is defined as at least one (1) of the following: 1) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments 2) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50 3) radiation-induced oophorectomy with last menses >1 year ago 4) chemotherapy-induced menopause with >1 year interval since last menses 5) surgical sterilisation (bilateral oophorectomy or hysterectomy) -Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. EXCLUSION CRITERIA: -Patients who have had prior treatment with olaparib or any other PARPi -Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated. -Persistent toxicities (>= CTCAE grade 2) with the exception of alopecia or peripheral neuropathy, caused by previous cancer therapy. -Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility. -Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days. -History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib. -Patients receiving strong or moderate CYP3A inhibitors or inducers are ineligible. A washout period prior to the first dose of olaparib for patients on CYP3A inhibitors/inducers is 5 half-lives or 3 weeks, whichever is shorter. Medications with limited systemic absorption (e.g., ophthalmic, otic) do not require a washout and are permitted. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference texts such as the Physicians Desk Reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. -Pregnant women are excluded from this study because olaparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects. -Any chronic or concurrent acute liver disease. -History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to enrollment. -Uncontrolled concurrent disease or illness including but not limited to: --ongoing or active infection --symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia --unstable or untreated cardiac conditions or ejection fraction of <50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) --uncontrolled diabetes mellitus --psychiatric illness/social situations that would limit compliance with study requirements -Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study. -Immunocompromised patients, e.g., those with known HIV not on HAART with detectable levels of virus. -Patients with known active hepatitis (i.e., hepatitis B or C) -Other malignancy within the last two (2) 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, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >=5 years. Patients with a history of localized triple negative breast cancer or localized resected prostate cancer may be eligible, provided they completed their adjuvant chemotherapy more than two (2) years prior to registration, and that the patient remains free of recurrent or metastatic disease. -Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment -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)
-Patients must have a histologically confirmed diagnosis non prostate GU cancer.
-Patients with the presence of cancer-associated genetic mutations in one or more pathogenic or likely pathogenic gene alterations tested in the FoundationOne FoundationOne(Registered Trademark)CDx (F1CDx) panel will be enrolled in Cohorts 1 or 2 as follows:
--Cohort 1: BRCA1, BRCA2, ATM, BAP1, PALB2, and BRIP1, or tumor mutational burden (TMB) where 10 or greater mutations/megabase.
--Cohort 2:
ABL1 FANCE POLD1
ATR FANCG POLE
ATRX FANCL RAD51
BARD1 IKBKE SMARCB1
BRD4 MEN1 STK11
CCND1 MLH1 TP53
CHEK1 MSH2
CHEK2 MSH6
DOT1L MUTYH
FANCA NPM1
FANCC PMS2
-Patients with benign or variants of unknown significance as determined by FoundationOne FoundationOne (Registered Trademark) CDx (F1CDx) panel and Genetics Review Panel review will be enrolled in Cohort 3 to be followed for survival.
-Foundation One mutation analysis results performed prior to enrollment on this study may be accepted for eligibility review and in the event that a patient cannot undergo a biopsy and tumor is not available, Foundation Medicine liquid biopsy may be performed.
-Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm (greater than or equal to 2 cm) by chest x-ray or as greater than or equal to 10 mm (greater than or equal to 1 cm) with CT scan, MRI, or calipers by clinical exam.
-Evidence of disease progression as defined by RECIST (version 1.1) during treatment or after the most recent dose of therapy with at least one platinum-based regimen of chemotherapy and/or an immune-checkpoint inhibitor (atezolizumab, pembrolizumab, nivolumab, avelumab or durvalumab) (2-week washout from chemotherapy and 4-weeks washout from monoclonal antibodies is required).
-Age greater than or equal to 18 years.
Because no dosing or adverse event data are currently available on the use of olaparib in patients <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
-ECOG performance status less than or equal to 1 (or Karnofsky greater than or equal to 70%).
-Patients must have normal organ and marrow function as defined below:
--leukocytes greater than or equal to 3,000/mcL
--absolute neutrophil count greater than or equal to 1,500/mcL
--platelets greater than or equal to 100,000/mcL
--total bilirubin less than or equal to 1.5 x ULN (for subjects with documented Gilbert s disease total bilirubin less than or equal to 3.0 mg/dL)
--AST(SGOT)/ALT(SGPT) less than or equal to 2.5 x institutional upper limit of normal (for subjects with liver metastasis AST/ALT less than or equal to 5x ULN)
--creatinine clearance greater than or equal to 50 mL/min/1.73 m^2
--hemoglobin greater than or equal to 10 g/dL; transfusions are allowed
--PT/INR and aPTT Within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on direct oral anticoagulant (DOA)
-Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of olaparib.
-Pre-clinical data indicate that olaparib adversely affects embryofetal survival and development. Therefore, women of child-bearing potential and their partners should agree to use two (2) highly effective forms of contraception throughout study participation and for at least six (6) months after the last dose of olaparib. Male study participants should avoid fathering a child or donating sperm during the study and for three (3) months after the last dose of olaparib.
Note: Olaparib is a PARP inhibitor with the potential for teratogenic or abortifacient effects.
Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib.
-Ability to understand and the willingness to sign a written informed consent document or patients with Impaired Decision Making Capacity (IDMC) if they are represented by a Legally Authorized Representative (LAR).
-Patients must provide archival tumor sample for mutation analysis or be willing to undergo screening biopsy. In the event that a patient cannot undergo biopsy and tumor is not available, Foundation Medicine liquid biopsy will be performed.
-Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment at screening. Note: This will also need to be confirmed within 3 days prior to treatment on day 1.
Postmenopausal is defined as at least one (1) of the following:
1) Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
2) Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
3) radiation-induced oophorectomy with last menses >1 year ago
4) chemotherapy-induced menopause with >1 year interval since last menses
5) surgical sterilisation (bilateral oophorectomy or hysterectomy)
-Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
EXCLUSION CRITERIA:
-Patients who have had prior treatment with olaparib or any other PARPi
-Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline features suggestive of myelodysplastic syndrome or acute myelogenous leukemia on peripheral blood smear or bone marrow biopsy, if clinically indicated.
-Persistent toxicities (>= CTCAE grade 2) with the exception of alopecia or peripheral neuropathy, caused by previous cancer therapy.
-Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility.
-Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib.
-Patients receiving strong or moderate CYP3A inhibitors or inducers are ineligible. A washout period prior to the first dose of olaparib for patients on CYP3A inhibitors/inducers is 5 half-lives or 3 weeks, whichever is shorter. Medications with limited systemic absorption (e.g., ophthalmic, otic) do not require a washout and are permitted.
Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference texts such as the Physicians Desk Reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
-Pregnant women are excluded from this study because olaparib is a PARP inhibitor agent with the potential for teratogenic or abortifacient effects.
-Any chronic or concurrent acute liver disease.
-History of stroke, transient ischemic attack (TIA), or myocardial infarction, within 6 months prior to enrollment.
-Uncontrolled concurrent disease or illness including but not limited to:
--ongoing or active infection
--symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia
--unstable or untreated cardiac conditions or ejection fraction of <50% as determined by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
--uncontrolled diabetes mellitus
--psychiatric illness/social situations that would limit compliance with study requirements
-Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
-Immunocompromised patients, e.g., those with known HIV not on HAART with detectable levels of virus.
-Patients with known active hepatitis (i.e., hepatitis B or C)
-Other malignancy within the last two (2) 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, or other solid tumours including lymphomas
(without bone marrow involvement) curatively treated with no evidence of disease for >=5 years. Patients with a history of localized triple negative breast cancer or localized resected prostate cancer may be eligible, provided they completed their adjuvant chemotherapy
more than two (2) years prior to registration, and that the patient remains free of recurrent or metastatic disease.
-Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 2 weeks prior to study treatment
-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)
Principal Investigator
Referral Contact
For more information: