VX-970 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery



Status:Recruiting
Healthy:No
Age Range:18 - Any
Updated:2/17/2019
Start Date:June 8, 2016

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

This phase I trial studies the side effects and best dose of ATR kinase inhibitor M6620
(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. VX-970 and irinotecan hydrochloride may stop the
growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of
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. 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 M6620 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.

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 other systemic therapy or radiotherapy or
patients who have not recovered from adverse events due to prior administered agents
as follows:

- Chemotherapy < 4 weeks prior to entering the study

- Radiotherapy < 4 weeks prior to entering the study

- Nitrosoureas/mitomycin C < 6 weeks prior to entering the study

- Targeted therapy < 2 weeks (or 5 half-lives, whichever is longer) prior to
entering the study

- Those who have not recovered from clinically significant adverse events due to
prior agents administered to grade =< 1 or baseline, with exception of alopecia
and peripheral neuropathy, unless approved by the protocol chair

- 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.) should be avoided; 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
We found this trial at
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New Haven, Connecticut 6520
(203) 432-4771
Principal Investigator: Joseph P. Eder
Phone: 203-785-5702
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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75 Francis street
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Geoffrey I. Shapiro
Phone: 888-823-5923
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Principal Investigator: Geoffrey I. Shapiro
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55 Fruit St
Boston, Massachusetts 02114
(617) 724-4000
Principal Investigator: Geoffrey I. Shapiro
Phone: 877-726-5130
Massachusetts General Hospital Cancer Center An integral part of one of the world
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Geoffrey I. Shapiro
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Chapel Hill, North Carolina 27599
Principal Investigator: Elizabeth C. Dees
Phone: 877-668-0683
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10 Barnes West Drive
Creve Coeur, Missouri 63141
Principal Investigator: Saiama N. Waqar
Phone: 800-600-3606
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4160 John R St #2122
Detroit, Michigan 48201
(313) 833-1785
Principal Investigator: Ulka N. Vaishampayan
Phone: 313-576-9790
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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1600 Southwest Archer Road
Gainesville, Florida 32610
Principal Investigator: Thomas J. George
Phone: 352-273-8010
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1983 Marengo St
Los Angeles, California 90033
(323) 226-2622
Principal Investigator: Anthony El-Khoueiry
Phone: 323-865-0451
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1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
Principal Investigator: Anthony El-Khoueiry
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U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
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Nashville, Tennessee 37232
Principal Investigator: Elizabeth J. Davis
Phone: 800-811-8480
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New Haven, Connecticut 06510
Principal Investigator: Joseph P. Eder
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875 Blake Wilbur Drive
Palo Alto, California 94304
Principal Investigator: Shivaani Kummar
Phone: 650-498-7061
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Pasadena, California 91105
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Pittsburgh, Pennsylvania 15232
Principal Investigator: Liza C. Villaruz
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Sacramento, California 95817
Principal Investigator: Karen L. Kelly
Phone: 916-734-3089
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: Saiama N. Waqar
Phone: 800-600-3606
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Saint Louis, Missouri 63129
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11155 Dunn Road
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150 Entranceway Drive
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Principal Investigator: Rahul R. Aggarwal
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