M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
This phase I trial studies the side effects and best dose of M6620 and irinotecan hydrochloride in treating patients with solid tumors that have spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). M6620 and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Stanford is currently not accepting patients for this trial.
Intervention(s):
- drug: Irinotecan Hydrochloride
- drug: Berzosertib
- procedure: Biopsy Specimen
- procedure: Biospecimen Collection
- procedure: Computed Tomography
Eligibility
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
- FOR PATIENTS ENROLLED IN THE EXPANSION COHORT: Patients must have known deficiencies
in the deoxyribonucleic acid (DNA)-Damage Response (DDR), e.g. mutations in ATM,
PALB2, BRCA1/2 or other deficiencies after discussion with the Study Chair
(prioritized), or patients can be enrolled with the following tumor types regardless
of known DDR deficiency: pancreatic cancer, colorectal cancer, and small cell lung
cancer
- 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 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
- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of M6620 (VX-970, berzosertib) in combination with irinotecan in patients < 18
years of age, children are excluded from this study, but will be eligible for future
pediatric trials
- 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 -13, approximately 18 to 22 hours post end of irinotecan infusion and
day 2, approximately 18 to 22 hours post end of irinotecan infusion [= 17 to 21 hours
post end of M6620 (VX-970, berzosertib)]); patients enrolled to this cohort should
have tumors deemed easily accessible for biopsies with low likelihood of complication
- The effects of M6620 (VX-970, berzosertib) on the developing human fetus are unknown;
for this reason and because DNA-damage response (DDR) inhibitors may have teratogenic
potential, 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 M6620 (VX-970,
berzosertib) administration
- For this reason and because DNA-damage response (DDR) inhibitors may have
teratogenic potential, 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
- Immunotherapy < 4 weeks prior to entering the study
- 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 M6620 (VX-970, berzosertib) or irinotecan
- M6620 (VX-970, berzosertib) is primarily metabolized by CYP3A4; irinotecan and its
active metabolite, SN-38, are metabolized by CYP3A4 and UGT1A1, respectively;
therefore, concomitant administration with strong inhibitors or inducers of CYP3A4
should be avoided; valproic acid is known to inhibit the process of glucuronidation
and may potentially enhance the toxicity of irinotecan; 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 because M6620 (VX-970, berzosertib) as a
DNA-damage response (DDR) inhibitor may have the potential for teratogenic or
abortifacient effects; because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with M6620 (VX-970,
berzosertib), breastfeeding should be discontinued if the mother is treated with M6620
(VX-970, berzosertib); these potential risks may also apply to other agents used in
this study
- 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 because of the potential for pharmacokinetic interactions with
M6620 (VX-970, berzosertib); patients with poorly controlled HIV are not eligible due
to the increased risk of lethal infections when treated with marrow-suppressive
therapy
Ages Eligible for Study
18 Years - N/A
Genders Eligible for Study
All
Not currently accepting new patients for this trial
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
CCTO
650-498-7061
Not Recruiting
Our research team includes physicians, residents, medical students, research assistants, and volunteers. Our research topics include medical imaging, device validation, mobile application development, and pharmaceutical trials.
Some of the Neuro-Opthalmic concerns we investigate include Multiple Sclerosis, Optic Neuritis, IIH, and ICP.