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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started
Principal Investigator
Rahul R. Aggarwal

Description

Summary

This phase I trial studies the side effects and best dose of ATR kinase inhibitor VX-970 and irinotecan hydrochloride 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.

Official Title

Phase I Clinical Trial of VX-970 in Combination With the Topoisomerase I Inhibitor Irinotecan in Patients With Advanced Solid Tumors

Details

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ATR kinase inhibitor VX-970 (VX-970) in combination with irinotecan hydrochloride (irinotecan) in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

I. To estimate the safety and tolerability of VX-970 in combination with irinotecan.

II. To document anti-tumor activity. Anti-tumor activity will be measured by overall response rate (ORR) and progression-free survival (PFS).

III. To determine the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of VX-970 and irinotecan.

TERTIARY OBJECTIVES:

I. To identify molecular subpopulations of patients with increased sensitivity to the irinotecan and VX-970 combination.

OUTLINE: This is a dose-escalation study.

Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and ATR kinase inhibitor VX-970 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days, then at 3 and 6 months.

Keywords

Advanced Malignant Solid Neoplasm Metastatic Malignant Neoplasm Metastatic Malignant Solid Neoplasm Refractory Malignant Neoplasm Unresectable Malignant Neoplasm Unresectable Solid Neoplasm Irinotecan Camptothecin Topoisomerase I Inhibitors

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • Stanford Cancer Institute accepting new patients
    Palo Alto, California, 94304, United States
  • University of California Davis Comprehensive Cancer Center accepting new patients
    Sacramento, California, 95817, United States
  • Keck Medical Center of USC Pasadena accepting new patients
    Pasadena, California, 91105, United States
  • Los Angeles County-USC Medical Center accepting new patients
    Los Angeles, California, 90033, United States
  • USC / Norris Comprehensive Cancer Center accepting new patients
    Los Angeles, California, 90033, United States

Details

Status
accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT02595931
Phase
Phase 1
Lead Scientist
Rahul R. Aggarwal
Study Type
Interventional
Last Updated
May 1, 2017