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

Conditions

• Advanced Breast Carcinoma
• Advanced Colon Carcinoma
• Advanced Colorectal Carcinoma
• Advanced Endometrial Carcinoma
• Advanced Gastric Carcinoma
• Advanced Gastroesophageal Junction Adenocarcinoma
• Advanced Malignant Solid Neoplasm
• Advanced Salivary Gland Carcinoma
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Clinical Stage III Gastric Cancer AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IV Gastric Cancer AJCC v8
• Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
• HER2-Positive Breast Carcinoma
• Malignant Hepatobiliary Neoplasm
• Metastatic Breast Carcinoma
• Metastatic Colon Carcinoma
• Metastatic Colorectal Carcinoma
• Metastatic Endometrial Carcinoma
• Metastatic Gastric Carcinoma
• Metastatic Gastroesophageal Junction Adenocarcinoma
• Metastatic Malignant Solid Neoplasm
• Metastatic Salivary Gland Carcinoma
• Stage III Colon Cancer AJCC v8
• Stage III Colorectal Cancer AJCC v8
• Stage III Major Salivary Gland Cancer AJCC v8
• Stage III Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
• Stage IV Colon Cancer AJCC v8
• Stage IV Colorectal Cancer AJCC v8
• Stage IV Major Salivary Gland Cancer AJCC v8
• Stage IV Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8
• Unresectable Breast Carcinoma
• Unresectable Colon Carcinoma
• Unresectable Colorectal Carcinoma
• Unresectable Endometrial Carcinoma
• Unresectable Gastric Carcinoma
• Unresectable Gastroesophageal Junction Adenocarcinoma
• Unresectable Malignant Solid Neoplasm
• Unresectable Salivary Gland Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo tissue biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Ceralasertib — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo CT or PET/CT
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Positron Emission Tomography — PROCEDURE
  Undergo PET/CT
• Trastuzumab Deruxtecan — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Aug 9, 2021

Status verified

Apr 2026

Primary completion

Mar 31, 2027

Completion

Mar 31, 2027

Study Design

Enrollment

51 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Treatment (trastuzumab deruxtecan, ceralasertib)
  Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: During the dose-expansion phase, the first 6 patients in each disease cohort (gastroesophageal cancer \[cohort A\] and colorectal cancer \[cohort B\]) receive only trastuzumab deruxtecan for the first cycle, followed by trastuzumab deruxtecan and ceralasertib together in subsequent cycles. Additionally, patients undergo tissue biopsy on study and blood sample collection, CT or PET/CT and ECHO or MUGA throughout the study.

Primary Outcome Measure

Incidence of adverse events (Dose escalation phase) [ Time Frame: Up to 5 years ]

Locations (23)

Find similar trials in Irvine, CA

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