This study is currently recruiting participants.
Number
000692-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 12 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
None
Keywords
PARP Inhibitor; Dna Damaging Agent; Dna Alkylating Agent; Solid Tumor
Recruitment Keyword(s)
Condition(s)
Solid Tumors
Investigational Drug(s)
Talazoparib
Investigational Device(s)
Intervention(s)
Drug: Temozolomide Drug: Talazoparib
Supporting Site
National Cancer Institute
Rare tumors are a group of cancers with limited treatment options and poor outcomes. Researchers want to see if a pair of drugs (talazoparib and temozolomide) used together can help.
Objective:
To find whether talazoparib and temozolomide can shrink or stabilize some rare tumors.
Eligibility:
People aged 12 and older who have a confirmed rare solid tumor. The tumor must have progressed on standard therapy. Or, it must be a tumor for which no standard treatments exist.
Design:
Participants will first be screened with the following:
Physical exam
Medical history
Blood and urine tests
Assessment of how they are doing with their daily living activities
Imaging scans, including CT, PET, or MRI
Heart tests
Optional tumor biopsy
Both study drugs are pills taken by mouth. Participants will take them on a 28-day cycle. They will take talazoparib every day for 28 days. They will take temozolomide on days 2 through 6 of each cycle. They will keep a pill diary to help keep track of when they take their pills. They will come to a clinic on days 1, 8, and 22 of each cycle. Some tests will be repeated at each clinic visit.
Imaging scans will be repeated after every 2 cycles. Participants may have an additional optional tumor biopsy at the beginning of cycle 3.
Participants will continue taking the study drugs until their cancer gets worse or the side effects get bad.
Participants who stop taking the study drugs will receive a follow-up call after 30 days.
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INCLUSION CRITERIA: Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no longer standard of care therapy. -Patients must not be eligible for a higher priority study, such as a disease specific study of phase 2 or higher or a randomized study. Specifically, patients with pheochromocytoma and paraganglioma at the Clinical Center will be eligible for this study if they are not eligible for the NCT04394858 due to prior PARP inhibitor, DTIC or temozolomide therapy. Patients must have measurable disease as defined by RECIST v1.1, with 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). Patients consenting to biopsies must have a tumor site amenable to biopsy If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurement. Prior to entering the study, patients must have: - >= 3 weeks since completion of radiation therapy or major surgery - >= 5 half-lives or 3 weeks (whichever is shorter) since completion of biologic therapy or chemotherapy -- Should be at least 6 weeks out from nitrosoureas and mitomycin C - >= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study - >= 1 week from palliative radiation therapy (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI s discretion). - recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted. Adults age >=18 years; children/adolescents age >=12 years to 17 years with BSA>=1.5 m^2. ECOG performance status <= 2 (Karnofsky >=60%). Patients must have normal organ and marrow function as defined below: Absolute neutrophil count >=1,500/mcL Platelets >=100,000/mcL Hemoglobin >=8 g/dL Total bilirubin <=1.5 X institutional upper limit of normal (<=3 (SqrRoot) upper limit of normal in the presence of documented Gilbert s syndrome or liver metastases at baseline) AST(SGOT)/ALT(SGPT) <=3 X ULN creatinine clearance >=60 mL/min/1.73 m^2 -creatinine for adult patients: <=1.5 X institutional ULN for pediatric patients (<18 years of age), serum creatinine must fit into one of the following categories: -<TAB>Patients 2 to <6 years, creatinine <= 0.8 mg/dL -<TAB>Patients 6 to <10 years, creatinine <= 1.0 mg/dL -<TAB>Patients 10 to <13 years, creatinine <= 1.2 mg/dL -<TAB>Male patients 13 to <16 years, creatinine <= 1.5 mg/dL -<TAB>Male patients 16 to <18 years, creatinine <= 1.7 mg/dL -<TAB>Female patients 13 to <18 years, creatinine <= 1.4 mg/dL Talazoparib and temozolomide can cause fetal harm based on animal reproductive and genetic toxicity studies. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 7 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration. Women of child-bearing potential must have a negative pregnancy test (urine or serum) in the 8 days prior to beginning treatment, and again on cycle 1 day 1 of treatment. Biopsies are optional on this study. In lieu of baseline biopsies, patients are encouraged to submit at registration archival tumor biopsy tissue from a previous research study or medical care providing it meets the minimum collection and preservations requirements outlined in Section 9.2.5. Criteria for the submission of archival tissue are: - Tissue must have been collected within 3 months prior to registration. - Patient must not have received any intervening therapy for their cancer since the collection of the tumor sample. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Sensory/motor neuropathy >= Grade 2 Patients who are receiving any other investigational agents. Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 1 month without requiring steroid and anti-seizure medication are eligible to participate History of allergic reactions attributed to compounds of similar chemical composition to study drugs. Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease. - Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. For these patients, HBsAg and anti-HBc tests must be done within 28 days prior to enrollment. - Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. For these patients, an HCV RNA test must be done within 28 days prior to enrollment. Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because temozolomide and talazoparib have demonstrated fetal harm in animal reproductive studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 months following the last dose of study drug.
Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no longer standard of care therapy.
-Patients must not be eligible for a higher priority study, such as a disease specific study of phase 2 or higher or a randomized study. Specifically, patients with pheochromocytoma and paraganglioma at the Clinical Center will be eligible for this study if they are not eligible for the NCT04394858 due to prior PARP inhibitor, DTIC or temozolomide therapy.
Patients must have measurable disease as defined by RECIST v1.1, with 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).
Patients consenting to biopsies must have a tumor site amenable to biopsy If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurement.
Prior to entering the study, patients must have:
- >= 3 weeks since completion of radiation therapy or major surgery
- >= 5 half-lives or 3 weeks (whichever is shorter) since completion of biologic therapy or chemotherapy
-- Should be at least 6 weeks out from nitrosoureas and mitomycin C
- >= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study
- >= 1 week from palliative radiation therapy (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI s discretion).
- recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted.
Adults age >=18 years; children/adolescents age >=12 years to 17 years with BSA>=1.5 m^2.
ECOG performance status <= 2 (Karnofsky >=60%).
Patients must have normal organ and marrow function as defined below:
Absolute neutrophil count >=1,500/mcL
Platelets >=100,000/mcL
Hemoglobin >=8 g/dL
Total bilirubin <=1.5 X institutional upper limit of normal (<=3 (SqrRoot) upper limit of normal in the presence of documented Gilbert s syndrome or liver metastases at baseline)
AST(SGOT)/ALT(SGPT) <=3 X ULN
creatinine clearance >=60 mL/min/1.73 m^2
-creatinine for adult patients:
<=1.5 X institutional ULN
for pediatric patients (<18 years of age), serum creatinine must fit into one of the following categories:
-<TAB>Patients 2 to <6 years, creatinine <= 0.8 mg/dL
-<TAB>Patients 6 to <10 years, creatinine <= 1.0 mg/dL
-<TAB>Patients 10 to <13 years, creatinine <= 1.2 mg/dL
-<TAB>Male patients 13 to <16 years, creatinine <= 1.5 mg/dL
-<TAB>Male patients 16 to <18 years, creatinine <= 1.7 mg/dL
-<TAB>Female patients 13 to <18 years, creatinine <= 1.4 mg/dL
Talazoparib and temozolomide can cause fetal harm based on animal reproductive and genetic toxicity studies. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 7 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration. Women of child-bearing potential must have a negative pregnancy test (urine or serum) in the 8 days prior to beginning treatment, and again on cycle 1 day 1 of treatment.
Biopsies are optional on this study. In lieu of baseline biopsies, patients are encouraged to submit at registration archival tumor biopsy tissue from a previous research study or medical care providing it meets the minimum collection and preservations requirements outlined in Section 9.2.5. Criteria for the submission of archival tissue are:
- Tissue must have been collected within 3 months prior to registration.
- Patient must not have received any intervening therapy for their cancer since the collection of the tumor sample.
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
Ability to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
Sensory/motor neuropathy >= Grade 2
Patients who are receiving any other investigational agents.
Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 1 month without requiring steroid and anti-seizure medication are eligible to participate
History of allergic reactions attributed to compounds of similar chemical composition to study drugs.
Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
- Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. For these patients, HBsAg and anti-HBc tests must be done within 28 days prior to enrollment.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. For these patients, an HCV RNA test must be done within 28 days prior to enrollment.
Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because temozolomide and talazoparib have demonstrated fetal harm in animal reproductive studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 months following the last dose of study drug.
Principal Investigator
Referral Contact
For more information: