Recruiting PHASE1 Clinical Stage III Gastric Cancer AJCC v8

New treatment option for Clinical Stage III Gastric Cancer AJCC v8

Official title Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors

ClinicalTrials.gov ID: NCT06364410

What this study is testing

What is Azenosertib?

Azenosertib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for clinical stage iii gastric cancer ajcc v8.

Also referred to as Wee1 Inhibitor ZN-c3, ZN c3.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), 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). Azenosertib is in a class of medications called kinase inhibitors.

Phase 1: an early, usually small safety study

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed...
HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing...
T-DXd (DS-8201a)-naive disease
In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction...
HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND

You likely can't join if

As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers...
Patients who are receiving any other investigational agents
Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs
Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying...
Patients who require supplemental oxygen for activities of daily living

See the full eligibility criteria

Who can join

In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic...
HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments [CLIA] platform...
T-DXd (DS-8201a)-naive disease
In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer that has progressed following at least one prior line of...
HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND
T-DXd (DS-8201a)-naive disease
Received prior trastuzumab-based treatment, if eligible for such treatment
For the dose escalation and dose expansion, patients can have evaluable or measurable disease
Potential trial participants should have recovered from clinically significant adverse events (AEs) of their most recent therapy/intervention prior to enrollment
Age ≥ 18 years. Because no dosing or AE data are currently available on the use of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3) in patients \< 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 (Karnofsky ≥ 70%). Both T-DXd (DS-8201a) and azenosertib (ZN-c3) have fatigue as an adverse effect. Due to the overlapping adverse effect, the...
Absolute neutrophil count ≥ 1.5 × 10\^9/L (within 7 days of study treatment initiation)
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Hemoglobin \> 9.0 g/dL (within 7 days of study treatment initiation)
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Platelets ≥ 100 × 10\^9/L (within 7 days of study treatment initiation)
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤ 3 × institutional ULN (within 7 days of study treatment initiation)
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Aspartate aminotransferase (AST [serum glutamic-oxaloacetic transaminase (SGOT)])/alanine aminotransferase (ALT [serum glutamate pyruvate transaminase (SGPT)]) ≤ 3 × institutional ULN. In the presence of liver...
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Measured of calculated creatinine clearance (CrCl) ≥ 60 mL/min (CrCl should be calculated per institutional standard; glomerular filtration rate can also be used in place of CrCl) ≥ 60 mL/min for patients with...
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
International normalized ratio/prothrombin time and activated partial thromboplastin time ≤ 1.5 × institutional ULN (within 7 days of study treatment initiation)
No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
No administration of granulocyte colony-stimulating factor is allowed within 1 week prior to screening assessment
Patients must have left ventricular ejection fraction (LVEF) ≥ 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment
Human immunodeficiency virus-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is...
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible for...
Life expectancy ≥ 3 months
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test result within 3 days of study treatment initiation
Agents composed of HER2 antibody conjugated to a topoisomerase 1 inhibitor and azenosertib (ZN-c3) are known to be teratogenic; thus, WOCBP must agree to use highly effective contraception from time of screening and...
Women of non-childbearing potential defined as premenopausal females with documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood...
Male patients involved with WOCBP must agree to use a highly effective form of contraception or avoid intercourse from time of screening and throughout the study treatment period and for at least 4 months after the last...
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Willing to undergo biopsy as required by the study (dose expansion only)
Note: Patients in the dose escalation who have insufficient/inadequate archival tissue may have optional pre-treatment biopsy
Patients must have adequate washout from prior therapy at the time of study treatment initiation: 4 weeks from major surgery (any surgical incision should be fully healed prior to study drug administration); 4 weeks...

What rules you out

As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers of CYP3A4 are prohibited with the exception of moderate or strong...
Patients who are receiving any other investigational agents
Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs
Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within 3 months of the study...
Patients who require supplemental oxygen for activities of daily living
Pregnant women are excluded from this study because T-DXd (DS-8201a) and azenosertib (ZN-c3) have the potential risk for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in...
Patients with history of non-infectious pneumonitis/interstitial lung disease (ILD), current ILD, or where suspected ILD cannot be ruled out by imaging at screening
Patients with active infections requiring treatment (antibiotic, antifungal, or antiviral) at the time of study treatment initiation are not eligible. Patients who have completed such treatment and whose infection is...
Patients with history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
Patients with current signs or symptoms of bowel obstruction including sub-occlusive disease related to underlying disease
Patients with a medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association class IIb to IV), and/or troponin levels consistent with...
Patients with clinically significant corneal disease
Patients with a pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART). (Drainage and CART are not allowed within 2...
Patients with history of Torsades de Pointes unless all risk factors that contributed to Torsades de Pointes have been corrected
Based on an average of triplicate 12-lead electrocardiogram (ECG), patients with a mean resting corrected QT (QTc) interval using Fridericia formula of \> 470 msec for both males and females at screening or a history of...
Patients with prior treatment with a WEE1 inhibitor (dose escalation and dose expansion)
Patients with prior treatment with T-DXd (DS-8201a) or other topoisomerase inhibitors (dose escalation and dose expansion)
Patients with uncontrolled intercurrent illness
Patients with prior allogeneic organ transplantation including allogeneic stem cell transplantation
Patients with clinically significant chronic gastrointestinal disorder with diarrhea as a major symptom; ≥ grade 2 diarrhea at baseline. Please contact the protocol principal investigator (PI) for any patient with more...
Patients with spinal cord compression

The study team makes the final eligibility decision.

Where it's taking place

Houston, Texas, United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.