This study is currently recruiting participants.
Number
001749-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women
Keywords
Precision Medicine; Combination Therapy; mutation of interest
Recruitment Keyword(s)
None
Condition(s)
Solid Tumors
Investigational Drug(s)
Nilotinib
Investigational Device(s)
Intervention(s)
Drug: Nilotinib/Paclitaxel
Supporting Site
National Cancer Institute
Multiple drugs used together are often more effective than using a single drug to treat cancers. The National Cancer Institute has compiled a database that compares results from 5000 pairs of approved drugs used to treat 60 types of cancers. Two of these drugs (nilotinib and paclitaxel) had never before been used together. The data suggest they may be effective when used together in people with cancer.
Objective:
To test nilotinib combined with paclitaxel in people with cancer.
Eligibility:
People aged 18 and older who have a solid tumor previously treated with a taxane drug. They must also be enrolled in the ComboMATCH Registration Protocol (EAY191).
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. They will have a sample of tissue removed from their tumor (biopsy); a recent biopsy sample may be used.
The study drugs will be given in 4-week cycles:
Nilotinib is a capsule by taken mouth. Participants will take this drug twice daily at home.
Paclitaxel is given through a tube attached to a needle inserted into a vein. Participants will receive paclitaxel weekly for the first 3 weeks of each 4-week cycle.
Imaging scans and other tests may be repeated during clinic visits.
Participants may continue treatment as long as the drugs are helping them and they are tolerating them.
When no longer receiving treatment, participants will have follow-up visits every 3 months for up to 2 years; then every 6 months in the third year. Follow-up visits may be in person or by phone.
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ELIGIBILITY CRITERIA: -Patient must fulfill all eligibility criteria outlined below and be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration to the EAY191-E4 study. This includes submission of NGS data from one of the MATCH Designated Laboratories for all potential participants prior to treatment protocol assignment. Copy number and allele frequency cutoffs as per the ComboMATCH Registration Protocol. -Patient must be >= 18 years of age. -Patient must not have any of the following mutations (as determined by the ComboMATCH Registration Protocol), which are known to confer sensitivity or resistance to nilotinib monotherapy: --KIT: W557R, V559D, V559A, L576P, and K642E --PDGFR-alpha: D842V -Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to EAY191-E4 registration. NOTE: The current actionable mutation of interest (aMOI)/actionable alteration list for this treatment trial can be found on the CTSU website: www.ctsu.org (final URL pending) NOTE: Novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol -Patient must be willing to provide blood samples for research purposes. -Patient must have had at least one prior line of therapy in the metastatic setting. -Patient must have previously undergone taxane therapy (in the metastatic setting). --Patients who previously responded to prior taxane therapy must have received their last dose of taxane therapy within 6 months prior to EAY191-E4 registration and have had no other intervening treatment prior to EAY191-E4 registration. --Patients who did not respond to prior taxane therapy are eligible regardless of the time elapsed since the prior taxane therapy or any other intervening therapies. -Patient must have an ECOG Performance Status of 0-2. -Patient must not have had platinum-resistant epithelial serous ovarian cancer. -Patient must not have peripheral neuropathy > grade 1. -Patient must not have sensory/motor neuropathy >= grade 2. -Patient must have documented QT interval with Fridericia s correction (QTcF) of <= 450 msec within 8 days prior to EAY191-E4 registration if they have a history of QTc prolongation, history of arrythmias, or are receiving medications that prolong QTc. Patients with congenital long QT syndrome are not eligible. -Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). Patient of child bearing potential? ______ (Yes or No) Date of blood test or urine study: ___________ -Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 3 months after the last dose of study drug. -Patients must have progressive disease. -Patients must have normal organ function as defined below: --Total bilirubin <=1.5 X institutional ULN (with the exception of those with Gilbert syndrome, who must have total bilirubin <=3 X institutional ULN) AST(SGOT)/ALT(SGPT) <=3.0 (SqrRoot) institutional ULN; < 5.0 x ULN in patients with liver metastases 5.0 x ULN in patients with liver metastases Creatinine <=1.5 X institutional ULN OR Creatinine clearance >=60 mL/min/1.73 m^2 for patients with creatinine levels >1.5 mg/dL -Patient must have the ability to swallow medications. -Patient must have completed any prior therapy >= 4 weeks or >= 5 halflive of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed (Bullet) 4 weeks prior to enrollment; prior palliative radiation should have been completed >= 2 weeks prior to enrollment. Patients must be >= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities. -Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for >=1 month after treatment of the brain metastases.
-Patient must fulfill all eligibility criteria outlined below and be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration to the EAY191-E4 study. This includes submission of NGS data from one of the MATCH Designated Laboratories for all potential participants prior to treatment protocol assignment. Copy number and allele frequency cutoffs as per the ComboMATCH Registration Protocol.
-Patient must be >= 18 years of age.
-Patient must not have any of the following mutations (as determined by the ComboMATCH Registration Protocol), which are known to confer sensitivity or resistance to nilotinib monotherapy:
--KIT: W557R, V559D, V559A, L576P, and K642E
--PDGFR-alpha: D842V
-Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to EAY191-E4 registration.
NOTE: The current actionable mutation of interest (aMOI)/actionable alteration list for this treatment trial can be found on the CTSU website: www.ctsu.org (final URL pending)
NOTE: Novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH Registration Protocol
-Patient must be willing to provide blood samples for research purposes.
-Patient must have had at least one prior line of therapy in the metastatic setting.
-Patient must have previously undergone taxane therapy (in the metastatic setting).
--Patients who previously responded to prior taxane therapy must have received their last dose of taxane therapy within 6 months prior to EAY191-E4 registration and have had no other intervening treatment prior to EAY191-E4 registration.
--Patients who did not respond to prior taxane therapy are eligible regardless of the time elapsed since the prior taxane therapy or any other intervening therapies.
-Patient must have an ECOG Performance Status of 0-2.
-Patient must not have had platinum-resistant epithelial serous ovarian cancer.
-Patient must not have peripheral neuropathy > grade 1.
-Patient must not have sensory/motor neuropathy >= grade 2.
-Patient must have documented QT interval with Fridericia s correction (QTcF) of <= 450 msec within 8 days prior to EAY191-E4 registration if they have a history of QTc prolongation, history of arrythmias, or are receiving medications that prolong QTc. Patients with congenital long QT syndrome are not eligible.
-Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
Patient of child bearing potential? ______ (Yes or No)
Date of blood test or urine study: ___________
-Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 3 months after the last dose of study drug.
-Patients must have progressive disease.
-Patients must have normal organ function as defined below:
--Total bilirubin <=1.5 X institutional ULN (with the exception of those with Gilbert syndrome, who must have total bilirubin <=3 X institutional ULN)
AST(SGOT)/ALT(SGPT) <=3.0 (SqrRoot) institutional ULN; < 5.0 x ULN in patients with liver metastases
5.0 x ULN in patients with liver metastases
Creatinine <=1.5 X institutional ULN
OR
Creatinine clearance >=60 mL/min/1.73 m^2 for patients with creatinine levels >1.5 mg/dL
-Patient must have the ability to swallow medications.
-Patient must have completed any prior therapy >= 4 weeks or >= 5 halflive of the prior agent (whichever is shorter) prior to enrollment on protocol. Prior definitive radiation should have been completed (Bullet) 4 weeks prior to enrollment; prior palliative radiation should have been completed >= 2 weeks prior to enrollment. Patients must be >= 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) and should have recovered to grade 1 or baseline from any toxicities.
-Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for >=1 month after treatment of the brain metastases.
Principal Investigator
Referral Contact
For more information: