Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene

Conditions

• Metastatic Malignant Solid Neoplasm
• Metastatic Pancreatic Adenocarcinoma
• Stage III Pancreatic Cancer AJCC v8
• Stage IV Pancreatic Cancer AJCC v8
• Unresectable Malignant Solid Neoplasm
• Unresectable Pancreatic Adenocarcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Computed Tomography — PROCEDURE
  Undergo CT scan
• Echocardiography Test — PROCEDURE
  Undergo echocardiography
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA scan
• Neratinib Maleate — DRUG
  Given PO
• Trastuzumab Deruxtecan — BIOLOGICAL
  Given IV

Study Details

This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable), and have changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to shrink cancer with a change in the HER2 gene.

Key Dates

First listed

May 13, 2022

Start date

Oct 5, 2022

Status verified

Jul 2026

Primary completion

Jul 17, 2028

Completion

Jul 17, 2028

Study Design

Enrollment

58 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Treatment (neratinib, trastuzumab deruxtecan)
  Patients receive neratinib PO QD on days 1-21 of each cycle (days 8-21 of cycle 1, then days 1-21 in cycles thereafter for PD cohort) and trastuzumab deruxtecan IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT scan and echocardiography or MUGA scan throughout study. Additionally, patients may undergo a tissue biopsy at baseline if no archival sample available (dose-escalation cohort only), optionally at baseline (pancreatic cohort only), on study (PD cohort only), and optionally at disease progression (all cohorts).

Primary Outcome Measure

Incidence of dose limiting toxicities (Part 1, Dose Escalation) [ Time Frame: In the first 2 cycles in dose escalation of combination of neratinib and trastuzumab deruxtecan (DS-8201a) (cycle length = 21 days) ]

Locations (18)

Find similar trials in Duarte, CA

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