M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Running, not enrolling · Phase 1

Conditions studied: Metastatic Colorectal Carcinoma, Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Solid Neoplasm, Metastatic Pancreatic Carcinoma, Refractory Colorectal Carcinoma, Refractory Lung Small Cell Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Pancreatic Carcinoma, Stage III Colorectal Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage III Pancreatic Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Colorectal Carcinoma, Unresectable Lung Small Cell Carcinoma, Unresectable Malignant Solid Neoplasm, Unresectable Pancreatic Carcinoma

In brief

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.

Key facts

Study ID: NCT02595931
Run by: National Cancer Institute (NCI)
People needed: 66
Starts: 2016-07-22
Expected to finish: 2027-03-06
Last updated by the study team: 2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

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
UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States
Vanderbilt Breast Center at One Hundred Oaks — Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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