A Study of ALRN-6924 for Protection of Chemotherapy-Induced Side Effects in Patients With TP53-Mutant Breast Cancer

NCT05622058 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: ALRN-6924-1-052022-000158-27
• Study Type: interventional
• Target: 6
• Locations: 4 countries
• Sites: 14

Brief Summary

This is a Phase 1b open-label, single arm, multicenter, study of ALRN-6924 as a chemoprotection agent in patients with TP53-mutated HER2- breast cancer (stages IIa to IIIb) receiving neoadjuvant or adjuvant chemotherapy with doxorubicin, docetaxel, and cyclophosphamide (TAC). Chemotherapy affects cells that are dividing, whether they are tumor cells or healthy cells (including, bone marrow cells, hair follicle cells, and epithelial cells lining the gastrointestinal tract). ALRN-6924 is designed to stop cell division in healthy cells but not in tumor cells because they have a mutation of the TP53 gene. When this happens, tumor cells will still be destroyed by the chemotherapy but healthy cells that are not dividing may be spared from chemotherapy damage and the patient should have less side effects.

Conditions

Prevention of Chemotherapy-induced Myelosuppression

Keywords

ALRN-6924; Chemoprotection; Myelosuppression; Cell cycle arrest; p53 mutation; Breast cancer; Alopecia; Neutropenia

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of ALRN-6924 in combination with TAC chemotherapy

  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

• Chemoprotective effects of ALRN-6924 on bone marrow toxicities

  Incidence and duration of Grade 4 neutropenia in Cycle 1 for each treatment cycle and all cycles combined

  Approximately 3 weeks for each patient

Secondary Outcomes (17)

• Chemoprotective effects of ALRN-6924 on alopecia induced by TAC

  Approximately 24 weeks

• Chemoprotective effects of ALRN-6924 on neutropenia

  Approximately 24 weeks

• Time to absolute neutrophil count (ANC) recovery in Cycle 1

  3 weeks (cycle 1)

• Depth of ANC nadir in Cycle 1

  3 weeks (cycle 1)

• Chemoprotective effects of ALRN-6924 on Grade ≥3 neutropenia for each cycle and all cycles

  Approximately 24 weeks

Study Arms (1)

ALRN-6924 Dose plus TAC

EXPERIMENTAL

ALRN-6924 plus Docetaxel, Doxorubicin, and Cyclophosphamide (TAC)

Drug: ALRN-6924; Drug: TAC (doxorubicin 50 mg/m2; cyclophosphamide 500 mg/m2; docetaxel 75 mg/m2)

Interventions

ALRN-6924 DRUG

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).

ALRN-6924 Dose plus TAC

TAC (doxorubicin 50 mg/m2; cyclophosphamide 500 mg/m2; docetaxel 75 mg/m2) DRUG

TAC will be administered as an IV infusion on Day 1 of every 3-week treatment cycle

ALRN-6924 Dose plus TAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Known hypersensitivity to any component of study treatment.
• Prior chemotherapy for HER2 negative breast cancer.
• \. 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.

Sponsors & Collaborators

• Aileron Therapeutics, Inc.: lead

Study Sites (14)

Oncology and Hematology Associates of West Broward

Tamarac, Florida, 33321, United States

Location

Southern Oncology Specialists

Huntersville, North Carolina, 28078, United States

Location

Regional Medical Oncolgy Center

Wilson, North Carolina, 27893, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Pennsylvania Cancer Specialists & Resesrach Institute

Gettysburg, Pennsylvania, 17325, United States

Location

University Clinical Center of the Republic of Srpska

Banja Luka, 71000, Bosnia and Herzegovina

Location

University Clinical Hospital Mostar

Mostar, 88000, Bosnia and Herzegovina

Location

Clinical Center University of Sarajevo, Oncology Clinic

Sarajevo, 71000, Bosnia and Herzegovina

Location

University Clinical Center Tuzla

Tuzla, 75000, Bosnia and Herzegovina

Location

MBAL University Hospital OOD

Panagyurishte, 4500, Bulgaria

Location

KOC (Complex Oncology Center) Plovdiv

Plovdiv, 4000, Bulgaria

Location

Kliničko bolnički centar "Bežanijska kosa"

Belgrade, 11070, Serbia

Location

Oncology Institute of Vojvodina

Kamenitz, 21204, Serbia

Location

Univerzitetski Klinički centar Kragujevac

Kragujevac, 34000, Serbia

Location

MeSH Terms

Conditions

Breast Neoplasms; Alopecia; Neutropenia

Interventions

Doxorubicin; Cyclophosphamide; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Hypotrichosis; Hair Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: November 18, 2022
• Study Start: January 9, 2023
• Primary Completion: February 22, 2023
• Study Completion: February 22, 2023
• Last Updated: February 27, 2023

Record last verified: 2023-02

Locations

BO (4); SE (3); US (5); BU (2)