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Metastatic Colorectal CarcinomaPhase 1NCT02595931

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

A Phase 1 study testing Berzosertib, Biopsy Specimen and Biospecimen Collection in people with Metastatic Colorectal Carcinoma and Metastatic Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 23 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Berzosertib, Biopsy Specimen and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
23 sitesUnited States
Study dates
22 Jul 2016to 6 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • Keck Medical Center of USC Pasadena

    Pasadena, California, 91105

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

Other trials in United States

About this study

Official title: Phase I Clinical Trial of M6620 (VX-970, Berzosertib) 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 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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Berzosertib, Biopsy Specimen, Biospecimen Collection, Computed Tomography, Irinotecan Hydrochloride
Medical subject headings
Colorectal Neoplasms, Small Cell Lung Carcinoma, Neoplasm Metastasis, Pancreatic Neoplasms, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BerzosertibDrug

    Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970

    Given IV

  • Biopsy SpecimenProcedure or surgery

    Also called Biopsy Sample

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Correlative studies

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Irinotecan HydrochlorideDrug

    Also called Campto, Camptosar, Camptothecin 11, Camptothecin-11

    Given IV

Study groups in NCT02595931
Study groupRoleWhat they receive
Treatment (irinotecan, M6620)ExperimentalPatients 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.
Receives: Drug: Berzosertib; Procedure: Biopsy Specimen; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Irinotecan Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD)

    Will be defined as the highest dose level at which =< 20% patients experience dose limiting toxicity. A logistic regression model will be used to determine the MTD using all patients.

    Measured: Up to 28 days

  2. Recommended phase 2 dose (RP2D) of ATR kinase inhibitor M6620 (VX-970, berzosertib) and irinotecan hydrochloride

    The RP2D will be determined based on MTD and the feasibility of the administration.

    Measured: Up to 28 days

Secondary outcomes (6)

  1. Incidence of adverse events of M6620 (VX-970, berzosertib) and irinotecan hydrochloride

    Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A toxicity will be considered to be an adverse event that is possibly, probably or definitely related to treatment. The maximum grade of toxicity for each category of interest will be recorded for each patient, and the summary results will be tabulated by category, grade, and dose level. Serious (>= grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.

    Measured: Up to 6 months after completion of study treatment

  2. Overall response rate

    Will be evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. Tabulated by disease diagnosis and by dose level. Will also report the 95% confidence limits on the response rates. Will also report the response rate and confidence limits at that dose level separately.

    Measured: Up to 6 months after completion of study treatment

  3. Incidence of stable disease

    Tabulated by disease diagnosis and by dose level. Will also report the response rate and confidence limits at that dose level separately.

    Measured: Up to 6 months after completion of study treatment

  4. Progression-free survival

    Estimated using the Kaplan-Meier method and the corresponding 95% confidence interval will be provided.

    Measured: Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up 6 months after completion of study treatment

  5. Pharmacokinetic parameters of M6620 (VX-970, berzosertib) in combination with irinotecan hydrochloride

    Within-subject comparison of day 15 and day -14 irinotecan hydrochloride and SN38 area under the curve (AUC) and half-life (t1/2) will be performed. Maximum concentration (Cmax), AUC, t1/2, clearance (CL), and volume in steady state (Vss) of VX-970 with single-agent historical data at comparable doses will be compared. Induction of gamma H2AX as a marker of ATR-dependent replication stress in peripheral blood mononuclear cells (PBMCs) and tumor will be characterized.

    Measured: Days -14 through -11, 1, 2, and 15 through 18 of cycle 1 (each cycle = 28 days)

  6. Pharmacodynamic parameters of M6620 (VX-970, berzosertib) in combination with irinotecan hydrochloride

    Within-subject comparison of day 15 and day -14 irinotecan hydrochloride and SN38 AUC and t1/2 will be performed. Cmax, AUC, t1/2, CL, and Vss of VX-970 with single-agent historical data at comparable doses will be compared. Induction of gamma H2AX as a marker of ATR-dependent replication stress in PBMCs and tumor will be characterized.

    Measured: Up to day 15 of cycle 1 (each cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2015 (estimated)
  2. Study start22 Jul 2016
  3. Primary completion7 Mar 2023
  4. Study completion6 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02595931
Sponsor's protocol ID
NCI-2015-01915
Other IDs
NCI-2015-01915, HCC 15-164, UPCI 15-164, HCC#15-164, 9938, 9938, UM1CA186689, UM1CA186690
Status last verified
Sep 2026
First submitted
3 Nov 2015
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Berzosertib, Biopsy Specimen and Biospecimen Collection in people with Metastatic Colorectal Carcinoma and Metastatic Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 23 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02595931.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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