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RecruitingPhase 1NCT04704661

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Phase 1/1B Study of DS-8201a in Combination With ATR Inhibition (AZD6738) in Advanced Solid Tumors With HER2 Expression (DASH Trial)

Sponsor

National Cancer Institute (NCI)

Enrollment

51 participants

Start Date

Aug 9, 2021

Study Type

INTERVENTIONAL

Conditions

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Breast CarcinomaClinical Stage III Gastric Cancer AJCC v8Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IV Gastric Cancer AJCC v8Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Metastatic Endometrial CarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaMetastatic Malignant Solid NeoplasmUnresectable Endometrial CarcinomaUnresectable Gastroesophageal Junction AdenocarcinomaUnresectable Malignant Solid NeoplasmStage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8HER2-Positive Breast CarcinomaMetastatic Gastric CarcinomaMetastatic Colorectal CarcinomaStage IV Colorectal Cancer AJCC v8Malignant Hepatobiliary NeoplasmUnresectable Breast CarcinomaStage III Colorectal Cancer AJCC v8Advanced Colorectal CarcinomaAdvanced Breast CarcinomaAdvanced Gastric CarcinomaAdvanced Malignant Solid NeoplasmAdvanced Endometrial CarcinomaAdvanced Colon CarcinomaAdvanced Gastroesophageal Junction AdenocarcinomaAdvanced Salivary Gland CarcinomaMetastatic Colon CarcinomaMetastatic Salivary Gland CarcinomaStage III Colon Cancer AJCC v8Stage III Major Salivary Gland Cancer AJCC v8Stage IV Colon Cancer AJCC v8Stage IV Major Salivary Gland Cancer AJCC v8Unresectable Colon CarcinomaUnresectable Colorectal CarcinomaUnresectable Gastric CarcinomaUnresectable Salivary Gland Carcinoma

Summary

The dose escalation phase of this trial identifies the safety, side effects and best dose of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib and trastuzumab deruxtecan may be safe, tolerable and effective in treating patients with advanced solid tumors expressing the HER2 protein or gene.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study (called the DASH trial) is testing the combination of two targeted drugs — DS-8201a (trastuzumab deruxtecan, a HER2-targeting antibody-drug conjugate) and AZD6738 (a DNA damage repair inhibitor) — in patients with advanced cancers that express the HER2 protein. It is testing safety and effectiveness in both a dose-finding phase and then in specific cancer types. **You may be eligible if...** - You are 18 or older - You have advanced/metastatic solid tumors (dose escalation phase), or specifically advanced gastroesophageal or colorectal cancer (dose expansion phase) - Your tumor expresses HER2 - You have adequate organ function **You may NOT be eligible if...** - You have already received DS-8201a and progressed on it - You have serious lung disease (interstitial lung disease) - Your overall health is too poor to tolerate treatment - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREBiopsy Procedure

Undergo tissue biopsy

PROCEDUREBiospecimen Collection

Undergo blood sample collection

DRUGCeralasertib

Given PO

PROCEDUREComputed Tomography

Undergo CT or PET/CT

PROCEDUREEchocardiography Test

Undergo ECHO

PROCEDUREMultigated Acquisition Scan

Undergo MUGA

PROCEDUREPositron Emission Tomography

Undergo PET/CT

BIOLOGICALTrastuzumab Deruxtecan

Given IV

Locations(23)

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Los Angeles General Medical Center

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Memorial Hospital East

Shiloh, Illinois, United States

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 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

NYP/Weill Cornell Medical Center

New York, New York, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Texas at Austin

Austin, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

University of Texas Medical Branch

Galveston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

View Full Details on ClinicalTrials.gov

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NCT04704661

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