- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05622058
A Study of ALRN-6924 for Protection of Chemotherapy-Induced Side Effects in Patients With TP53-Mutant Breast Cancer
A Phase 1b Clinical Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, as a Chemoprotection Agent in Patients With TP53-Mutated, HER2 Negative Breast Cancer Receiving Neoadjuvant or Adjuvant Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Andres Brainsky, MD
- Phone Number: 484-868-8286
- Email: abrainsky@aileronrx.com
Study Locations
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Banja Luka, Bosnia and Herzegovina, 71000
- University Clinical Center of the Republic of Srpska
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Mostar, Bosnia and Herzegovina, 88000
- University Clinical Hospital Mostar
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Sarajevo, Bosnia and Herzegovina, 71000
- Clinical Center University of Sarajevo, Oncology Clinic
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Tuzla, Bosnia and Herzegovina, 75000
- University Clinical Center Tuzla
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Panagyurishte, Bulgaria, 4500
- MBAL University Hospital OOD
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Plovdiv, Bulgaria, 4000
- KOC (Complex Oncology Center) Plovdiv
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Belgrade, Serbia, 11070
- Klinicko Bolnicki Centar "Bezanijska Kosa"
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Kragujevac, Serbia, 34000
- Univerzitetski Klinicki centar Kragujevac
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Sremska Kamenica, Serbia, 21204
- Oncology Institute of Vojvodina
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Florida
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Tamarac, Florida, United States, 33321
- Oncology and Hematology Associates of West Broward
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North Carolina
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Huntersville, North Carolina, United States, 28078
- Southern Oncology Specialists
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Wilson, North Carolina, United States, 27893
- Regional Medical Oncolgy Center
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Ohio
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Canton, Ohio, United States, 44718
- Gabrail Cancer Center
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Pennsylvania
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Gettysburg, Pennsylvania, United States, 17325
- Pennsylvania Cancer Specialists & Resesrach Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Females and males, age ≥18years.
- Patients who, in the investigator's judgment, are able to understand and willing to comply with the requirements of this clinical trial and to provide written informed consent.
- Histologically confirmed diagnosis of HER2 negative breast cancer
- Candidate to receive chemotherapy with TAC regimen
- Presence of p53 mutation(s) in tumor tissue as assessed by next generation sequencing (NGS).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
- Left ventricular ejection fraction > 55%.
Laboratory results obtained within 14 days prior to the first study treatment administration (Cycle 1, Day 0) demonstrating:
- Absolute neutrophil count (ANC) ≥ 1500 cells/μL (without granulocyte colony stimulating factor [G-CSF] support within 2 weeks prior to the first study treatment administration)
- Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to the first study treatment administration)
- Hemoglobin ≥ 10.0 g/dL
- AST, ALT, and alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN)
- Serum bilirubin ≤ 1.5× ULN (patients with known Gilbert's disease who have serum bilirubin level ≤ 3× ULN may be enrolled.)
- Patients who are not receiving therapeutic anticoagulation: Calculated creatinine clearance (CrCl) ≥ 30 mL/min (Cockcroft-Gault formula).
- Have not received prior chemotherapy or targeted systemic therapy for their breast cancer.
Exclusion Criteria:
- Known hypersensitivity to any component of study treatment.
Prior chemotherapy for HER2 negative breast cancer.
1. Presence of distant metastases. Nodal involvement is acceptable.
Uncontrolled intercurrent illness including but not limited to:
Clinically significant, active, uncontrolled infection including human immunodeficiency virus (HIV), or hepatitis B or C
- Patients with HIV must be on effective antiretroviral therapy for ≥ 4 weeks prior to enrollment and have HIV viral load < 400 copies/mL, have had no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the past 12 months, and have CD4+ count ≥ 350 cells/μL.
- Patients with chronic hepatitis B virus (HBV) must be on antiviral therapy and have HBV viral load below the limits of detection.
- Patients with hepatitis C virus (HCV) must be on or have completed antiviral therapy and have an HCV viral load below the limits of detection.
- Uncontrolled hypertension
- Uncontrolled diabetes mellitus
- Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker.
- Pregnant or lactating women.
- Hereditary angioedema of any severity or severe or life-threatening angioedema due to any cause.
- Treatment with an investigational agent for any indication within the shorter of 14 days or 5 half-lives, if the half-life is known.
- The required use of any concomitant medications that are predominantly cleared by hepatobiliary transporters, OATP members OATP1B1 and OATP1B3, on the day of the first ALRN-6924 infusion to within 48 hours after the last ALRN-6924 infusion in a treatment cycle. This criterion does not apply to the patients in the control group.
- Other medications, severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.
- Clinically evident alopecia of any grade at screening.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ALRN-6924 Dose plus TAC
ALRN-6924 plus Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)
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ALRN-6924 administered in every chemotherapy treatment cycle as an IV infusion over 1 hour on Days 0 (approximately 18 hours prior to chemotherapy administration), 1 (approximately 1 hour prior to chemotherapy administration), and 2 (approximately 24 hours after the second infusion of ALRN-6924).
TAC will be administered as an IV infusion on Day 1 of every 3-week treatment cycle
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of ALRN-6924 in combination with TAC chemotherapy
Time Frame: Approximately 24 weeks
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Proportion of patients with Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs); proportion of patients with treatment-related adverse events and serious adverse events as assessed by NCI CTCAE v5.0 Clinical and laboratory adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). System Organ Class (SOC) and Preferred Term (PT) will be attached to the clinical database. AE severity will be graded using the CTCAE. All AEs will be summarized (incidence) and listed by the System Organ Class (SOC), preferred term, toxicity/severity grade, and causal relationship to study medication. In addition, separate summaries of SAEs and Grade 3 and 4 AEs will be presented. |
Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on bone marrow toxicities
Time Frame: Approximately 3 weeks for each patient
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Incidence and duration of Grade 4 neutropenia in Cycle 1 for each treatment cycle and all cycles combined |
Approximately 3 weeks for each patient
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Chemoprotective effects of ALRN-6924 on alopecia induced by TAC
Time Frame: Approximately 24 weeks
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Incidence of Grade 2 alopecia after treatment with ALRN-6924 plus TAC
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Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on neutropenia
Time Frame: Approximately 24 weeks
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Incidence rate of grade 4 neutropenia for each treatment cycle and all cycles combined
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Approximately 24 weeks
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Time to absolute neutrophil count (ANC) recovery in Cycle 1
Time Frame: 3 weeks (cycle 1)
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Time in days from ANC nadir to recovery
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3 weeks (cycle 1)
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Depth of ANC nadir in Cycle 1
Time Frame: 3 weeks (cycle 1)
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Lowest ANC count during cycle 1
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3 weeks (cycle 1)
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Chemoprotective effects of ALRN-6924 on Grade ≥3 neutropenia for each cycle and all cycles
Time Frame: Approximately 24 weeks
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CTCAE v5 grade 3 neutropenia
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Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on thrombocytopenia
Time Frame: Approximately 24 weeks
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CTCAE v5 grade ≥3 thrombocytopenia
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Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on anemia
Time Frame: Approximately 24 weeks
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CTCAE v5 grade ≥3 anemia
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Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on febrile neutropenia
Time Frame: Approximately 24 weeks
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Incidence of febrile neutropenia for each cycle and all cycles
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Approximately 24 weeks
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Chemoprotective effects of ALRN-6924 on the need for chemotherapy dose reductions
Time Frame: Approximately 24 weeks
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Number of dose reductions of chemotherapy due to chemotherapy-related toxicity for each cycle and all cycles
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Approximately 24 weeks
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Use of myeloid growth factors
Time Frame: Approximately 24 weeks
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Number of instances of granulocyte colony-stimulating factors (G-CSF) use to treat Grade 4 neutropenia for each cycle and all cycles
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Approximately 24 weeks
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Need for red blood cell transfusions
Time Frame: Approximately 24 weeks
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Number of red blood cell (RBC) transfusions during each cycle and all cycles
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Approximately 24 weeks
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Need for platelet transfusions
Time Frame: Approximately 24 weeks
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Number of platelet transfusions during each cycle and all cycles The ALRN-6924 PK profile with and without AC chemotherapy will be compared. |
Approximately 24 weeks
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PK of ALRN-6924
Time Frame: Cycle 1 (each cycle is 21 days)
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PK parameters (e.g., area-under-the-curve [AUC]) of ALRN-6924
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Cycle 1 (each cycle is 21 days)
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PK of ALRN-6924
Time Frame: Cycle 1 (each cycle is 21 days)
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PK parameters (e.g., maximum concentration [Cmax] of ALRN-6924
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Cycle 1 (each cycle is 21 days)
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PK of ALRN-6924
Time Frame: Cycle 1 (each cycle is 21 days)
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PK parameters (e.g., time of Cmax [tmax]) of ALRN-6924
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Cycle 1 (each cycle is 21 days)
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PK of ALRN-6924
Time Frame: Cycle 1 (each cycle is 21 days)
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PK parameters (e.g., half-life [t1/2]) of ALRN-6924
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Cycle 1 (each cycle is 21 days)
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Efficacy of chemotherapy
Time Frame: Approximately 24 weeks
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Tumor response after TAC chemotherapy: proportion of patients with pCR after completion of neoadjuvant chemotherapy and surgery, per local standard of care and institutional policies
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Approximately 24 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Docetaxel
- Cyclophosphamide
- Doxorubicin
Other Study ID Numbers
- ALRN-6924-1-05
- 2022-000158-27 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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