Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Patients undergo collection of blood and buccal samples before or after SOC biopsy or tumor resection. Patients undergo collection of tumor tissue at time of SOC biopsy or tumor resection. Patients' medical records are also reviewed. Patients' archived tissue or blood samples may also be collected.

Biopsy Specimen

Undergo collection of blood and buccal swab samples

Biospecimen Collection

Undergo collection of archived tissue and blood samples

Medical Chart Review

Clinical Trials Referral Office

Aaron S. Mansfield, M.D.

This study characterizes deoxyribonucleic acid (DNA) and proteomic (protein) changes in both biopsies and tumors removed during surgery of patients who have been diagnosed with aggressive/metastatic (that has spread to other places in the body) cancer in order to identify possible diagnostic markers and potential drugs for treating aggressive tumor types. Proteomic analyses include looking at the proteome, or all the proteins expressed, or made by DNA at a specific moment in time. Studying samples of blood, buccal (cheek), and tissue in the laboratory from patients undergoing surgical resection or biopsy may help doctors learn more about the changes that occur in the proteome, DNA alterations, and identify molecular biomarkers for which therapeutic drugs may exist. Studying the DNA in tumor tissue and in blood may also help researchers see if the tumor has important differences.

PRIMARY OBJECTIVES:

I. To understand the pathogenesis, molecular mechanisms, and disease processes of malignancies.

II. To examine the utility of integrated genomics for discovery of targets or pathways involved in tumor/malignancy progression of patients with malignancies.

III. To observe for any evidence of anti-tumor activity from treatment if selected based on integrated genomics.

IV. To create and offer opportunities for targeted individualized therapy based on the outcome of integrated genomics and micro-cancer modeling.

V. To determine the outcome of patients with malignancies who received targeted individualized therapy.

OUTLINE: This is an ancillary-correlative study.

Patients undergo collection of blood and buccal samples before or after standard of care (SOC) biopsy or tumor resection. Patients undergo collection of tumor tissue at time of SOC biopsy or tumor resection. Patients' medical records are also reviewed. Patients' archived tissue or blood samples may also be collected.

Examining Blood and Tissue Samples to Identify Diagnostic Markers in Patients With Metastatic Cancer Undergoing Tumor Removal

Integrated Genomics and Patient-Derived Cancer Models

identify molecular targets for which therapeutic drugs may exist

Mayo Clinic

Respiratory Tract (Lung and Bronchial) Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Pancreatic Neoplasms

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Pancreatic Cancer

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

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

Computed Tomography

Irinotecan Hydrochloride

Liza C Villaruz

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.

PRIMARY OBJECTIVE:

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.

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

Phase I Clinical Trial of M6620 (VX-970, Berzosertib) in Combination With the Topoisomerase I Inhibitor Irinotecan in Patients With Advanced Solid Tumors

Paired t tests will be used to compare biomarker levels before and after treatment. The Benjamini and Hochberg's procedure will be used to control the false discovery rate at 30%. A descriptive analysis of patient tumor genotype and response to therapy will be performed.

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.

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

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.

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.

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

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

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Examining Blood and Tissue Samples to Identify Diagnostic Markers in Patients With Metastatic Cancer Undergoing Tumor Removal	NCT05530759	Hematopoietic a... Metastatic Mali...	Biopsy Specimen Biospecimen Col... Biospecimen Col... Medical Chart R...	18 Years -	Mayo Clinic
M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery	NCT02595931	Metastatic Colo... Metastatic Lung... Metastatic Mali... Metastatic Panc... Refractory Colo... Refractory Lung... Refractory Mali... Refractory Panc... Stage III Color... Stage III Lung ... Stage III Pancr... Stage IV Colore... Stage IV Lung C... Stage IV Pancre... Unresectable Co... Unresectable Lu... Unresectable Ma... Unresectable Pa...	Berzosertib Biopsy Specimen Biospecimen Col... Computed Tomogr... Irinotecan Hydr...	18 Years -	National Cancer Institute (NCI)

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