M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery
NCT ID: NCT02595931
Last Updated: 2025-11-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
PHASE1
66 participants
INTERVENTIONAL
2016-07-22
2026-03-06
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Liposomal Irinotecan and Veliparib in Treating Patients With Solid Tumors
NCT02631733
Bortezomib With or Without Irinotecan in Treating Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
NCT00103259
Veliparib and Irinotecan Hydrochloride in Treating Patients With Cancer That Is Metastatic or Cannot Be Removed by Surgery
NCT00576654
7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)
NCT00031681
M6620 (VX-970) in Selected Solid Tumors
NCT03718091
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of M6620 (VX-970, berzosertib) in combination with irinotecan hydrochloride (irinotecan) in patients with advanced solid tumors.
SECONDARY OBJECTIVES:
I. To estimate the safety and tolerability of M6620 (VX-970, berzosertib) in combination with irinotecan.
II. To document anti-tumor activity. III. To determine the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of M6620 (VX-970, berzosertib) and irinotecan.
EXPLORATORY OBJECTIVE:
I. To identify molecular subpopulations of patients with increased sensitivity to the irinotecan and M6620 (VX-970, berzosertib) combination.
OUTLINE: This is a dose-escalation study.
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes and M6620 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood samples throughout the study and undergo CT at screening, throughout the study, and during follow up.
After completion of study treatment, patients are followed up for 30 days, then at 3 and 6 months.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment (irinotecan, M6620)
Patients receive irinotecan hydrochloride IV over 90 minutes and M6620 IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood samples throughout the study and undergo CT at screening, throughout the study, and during follow up.
Berzosertib
Given IV
Biopsy Specimen
Undergo biopsy
Biospecimen Collection
Correlative studies
Computed Tomography
Undergo CT
Irinotecan Hydrochloride
Given IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Berzosertib
Given IV
Biopsy Specimen
Undergo biopsy
Biospecimen Collection
Correlative studies
Computed Tomography
Undergo CT
Irinotecan Hydrochloride
Given IV
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Liza C Villaruz
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh Cancer Institute LAO
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCSF Medical Center-Mount Zion
San Francisco, California, United States
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States
Yale University
New Haven, Connecticut, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Siteman Cancer Center-South County
St Louis, Missouri, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
HCC 15-164
Identifier Type: -
Identifier Source: secondary_id
UPCI 15-164
Identifier Type: -
Identifier Source: secondary_id
HCC#15-164
Identifier Type: -
Identifier Source: secondary_id
9938
Identifier Type: OTHER
Identifier Source: secondary_id
9938
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2015-01915
Identifier Type: -
Identifier Source: org_study_id
NCI-2015-01915
Identifier Type: REGISTRY
Identifier Source: secondary_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.