ATR Kinase Inhibitor VX-970 and Irinotecan Hydrochloride combination for solid tumors that are metastatic or cannot be removed

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"Experimental targeted cancer therapy and chemotherapy combination for tumors that have returned, spread, or cannot be removed"
Age:
18 to 100 years old
Gender:
Any
Healthy Volunteers:
No
Keywords:
cancer, tumor
Type:
Drug study, Phase 1
Investigator:
Description
This phase I trial studies the side effects and best dose of ATR kinase inhibitor VX-970 (experimental targeted cancer therapy) and irinotecan hydrochloride (chemotherapy) in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or cannot be removed by surgery. ATR kinase inhibitor VX-970 and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
This study requires
Please contact for more details
Who can participate?
Inclusion Criteria:

- Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option

- 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 >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

- No limit on prior lines of therapy for metastatic disease; prior adjuvant or neoadjuvant chemotherapy does not count as a prior line of therapy as long as completion of the adjuvant or neoadjuvant therapy was more than 1 year prior to patient enrollment

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)

- Life expectancy of greater than 12 weeks

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN); if liver involvement, =< 5 x ULN

- Creatinine clearance >= 60 mL/min/1.73 m^2

- Patients must have archived tumor tissue from prior tumor biopsy or surgical resections available for submission that is sufficient to complete molecular profiling

- FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: willingness to undergo mandatory biopsies (day -14, approximately 4 hours post end of irinotecan infusion and day 1, approximately 4 hours post end of irinotecan infusion [= 3 hours post end of VX-970]); patients enrolled to this cohort should have tumors deemed easily accessible for biopsies with low likelihood of complication

- 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; 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 6 months after completion of VX-970 administration; 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, for the duration of study participation and for 6 months after study completion

- Ability to understand and willingness to sign a written informed consent document


Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from clinically significant adverse events due to prior agents administered to =< grade 1 or baseline with the exception of alopecia and peripheral neuropathy, unless approved by the protocol chair

- Patients with uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A cluster (UGT1A)1*1/*28 genotype or *28/*28 genotype

- Patients who are receiving any other investigational agents

- Patients with unstable brain metastases should be excluded; however, patients with known brain metastases may participate in this clinical trial if they are clinically stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are on a stable or decreasing dose of steroids for at least 14 days prior to trial treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to VX-970 or irinotecan

- Concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; ; medications that enhance glucuronidation (i.e. phenytoin, phenobarbital, carbamazepine, rifampin, etc.) may also enhance clearance of SN-38, which may possibly decrease efficacy; therefore, concomitant administration of these drugs should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; 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

- Uncontrolled intercurrent illness including, but not limited to, severe active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients with chronic viral hepatitis may participate in this clinical trial if they are clinically stable with acceptable liver function

- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with VX-970

- Human immunodeficiency virus (HIV)-positive patients with well-controlled disease, as determined by CD4 count and viral load, who are on antiretroviral therapy that does not contain a strong inducer or inhibitor of CYP3A4 (e.g. regimens containing ritonavir, cobicistat, efavirenz or etravirine) are allowed on trial; HIV-positive patients on combination antiretroviral therapy with strong inducers or inhibitors of CYP3A4 are ineligible; patients with poorly controlled HIV are not eligible
Benefits and risks of participating
Please contact for details
Resources
Schedule
Study duration and period
Treatment: Variable Follow up: Six months
Recruitment period
From Nov. 10, 2016
Location
UC Davis Comprehensive Cancer Center
2279 45th Street
Sacramento, CA 95817
Contact
Corinne Turrell
Research Topic
Conditions:
  • Advanced Malignant Solid Neoplasm
  • Metastatic Malignant Neoplasm
  • Metastatic Malignant Solid Neoplasm
  • Refractory Malignant Neoplasm
  • Unresectable Malignant Neoplasm
  • Unresectable Solid Neoplasm

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