A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04022876
• Other study ID #: ALRN-6924-1-03
• Status: Terminated
• Phase: Phase 1
• Start date: September 3, 2019
• Est. completion date: August 30, 2022

Study information

• Verified date: October 2022
• Source: Aileron Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1b, multicenter, 2-part study of ALRN-6924 for the prevention of chemotherapy-induced side effects. Part 1 SCLC is an open-label, multicenter study of ALRN-6924 for the prevention of chemotherapy-induced side effects in patients with p53-mutated ED SCLC undergoing 2nd-line treatment with topotecan. (Part 1 has completed enrollment). Part 2 NSCLC is a randomized, double-blind, placebo-controlled, multicenter study of ALRN-6924 for the prevention of chemotherapy-induced side effects in patients with p53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy.

Description:

During Part 1 SCLC, topotecan will be administered per standard practice on Days 1-5 of 21-day cycles. Patients will be randomized to receive 1 of 2 initial ALRN-6924 dose levels, to be administered prior to each planned topotecan dose. The incidence, severity and duration of hematologic toxicities, including neutropenia, thrombocytopenia, and febrile neutropenia, will be determined. The safety and tolerability of each ALRN-6924 dose level will be assessed during Part 1. ALRN-6924 is given either 24 hr or 6 hr prior to each topotecan administration. Part 2 NSCLC of the study will be conducted in two stages. In Stage 1, a total of 20 patients will be randomized 1:1 to receive (with or without immunotherapy) either carboplatin plus pemetrexed plus ALRN-6924 or carboplatin plus pemetrexed plus placebo. During Stage 1 of Part 2 NSCLC, two interim analyses will be conducted after 10 and 20 patients, respectively, have been evaluated. The purpose of the two interim analyses is to confirm safety and exclude futility. In Stage 2 of Part 2 NSCLC, an additional 40 patients will be randomized to treatment as described for Stage 1. Immunotherapy and/or bevacizumab may be used concurrently with chemotherapy and after completion of 1st-line treatment (i.e., for maintenance purposes) as per local standard of care. Time of administration of immunotherapy and/or bevacizumab relative to chemotherapy will follow local standards of care.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: August 30, 2022
• Est. primary completion date: July 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Phase 1b, Part 2 NSCLC Inclusion Criteria:

• Histopathological confirmation of Stage IV NSCLC of adenocarcinoma histology. Cytological diagnosis of NSCLC is acceptable if sufficient tumor tissue is available for p53 mutation analysis. FDA approved liquid biopsies are also acceptable.
• Presence of one or more p53 mutations.
• Measurable disease using RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Adequate hematological status.
• Adequate hepatic and renal function.

Phase 1b, Part 2 NSCLC Exclusion Criteria:

• Advanced NSCLC tumors with EGFR mutations or ALK re-arrangement or other actionable genetic aberrations for which an approved targeted treatment is available. Patients who received prior treatment with EGFR or ALK inhibitors or other systemic drugs or immunotherapy for NSCLC are not eligible.
• Patients who are candidates for anti-PD-1 monotherapy in 1st line advanced NSCLC (e.g. tumors with high PD-L1 expression).
• Presence of active central nervous system metastases and/or carcinomatous meningitis.
• Significant weight loss (=15% body weight) within the 4 weeks prior to enrollment.

Phase 1b, Part 1 SCLC Inclusion Criteria:

• Histopathological confirmation of ED SCLC that has recurred or been refractory to one line of treatment with standard platinum-based chemotherapy or immuno-chemotherapy. Patients who received immunotherapy after platinum-based chemotherapy are eligible.
• Presence of one or more p53 mutations.
• Measurable disease using RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Adequate hematological status.
• Adequate hepatic and renal function.

Phase 1b, Part 1 SCLC Exclusion Criteria:

• More than one line of prior chemotherapy for ED SCLC (prior immunotherapy is permitted, concurrent with or subsequent to first line chemotherapy).
• Presence of active central nervous system metastases and/or carcinomatous meningitis.
• Significant weight loss (=15% body weight) within the 4 weeks prior to enrollment.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Intervention

Drug:
• ALRN-6924
ALRN-6924 administered IV on Days 0-2 prior to carboplatin and pemetrexed administered IV on Day 1 of every 21-day cycle.
• Carboplatin
Carboplatin administered IV on Day 1 of every 21-day cycle.
• Pemetrexed
Pemetrexed administered IV on Day 1 of every 21-day cycle.
• Placebo
Placebo administered IV on Days 0-2 prior to carboplatin and pemetrexed administered IV on Day 1 of every 21-day cycle.
• ALRN-6924
ALRN-6924 administered IV on Days 0-4 prior to topotecan administered IV on Days 1-5 of every 21-day cycle.
• Topotecan
Topotecan administered IV on Days 1-5 of every 21-day cycle.

Locations

Country	Name	City	State
Bosnia and Herzegovina	University Clinical Center of the Republic of Srpska, Lung Clinic	Banja Luka
Bosnia and Herzegovina	Clinical Center University of Sarajevo, Oncology Clinic	Sarajevo
Germany	Charité Comprehensive Cancer Center Benjamin Franklin Hamato, Onkologische	Berlin
Germany	Universitaetsklinikum Heidelberg Thoraxklinik Heidelberg	Heidelberg
Germany	LMU Klinikum der Universitaet Muenchen, Respiratory Medicine and Thoracic Oncology, Campus Innenstandt	Muenchen
Germany	München Klinik Neuperlach, Klinik für Hamatologie und Onkologie, Studienburo Neuperlach/Harlaching	Muenchen
Italy	Istituto Romagnolo per lo Studio dei Tumori, Dino Amadori	Meldola
Italy	Azienda Ospedaliero, Universitaria di Modena, Policlinico di Modena	Modena
Italy	Istituto Nazionale Tumori di Napoli, IRCCS, Fondazione, G. Pascale	Napoli
Italy	Università degli Studi di Pavia, IRCCS, Fondazione, Policlinico San Matteo	Pavia
Italy	Azienda Unità Sanitaria Locale della Romagna, Ospedale Santa Maria delle Croci	Ravenna
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Poland	Szpital Kliniczny Przemienienia Panskiego	Poznan
Serbia	CHC Bezanijska Kosa	Belgrade
Serbia	University Clinical Centre of Serbia, Pulmonology Clinic	Belgrade
Serbia	Clinical Centre Nis, Clinic for Pulmonary Diseases	Niš
Serbia	Institute for Pulmonary Diseases of Vojvodina	Novi Sad
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	MD Anderson Cancer Center	Madrid
United States	Gabrail Cancer Institute	Canton	Ohio
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Arizona Cancer Center	Kingman	Arizona
United States	Mount Sinai Cancer Research Program	Miami	Florida
United States	OSHU CHO Northwest	Portland	Oregon
United States	Oncology & Hematology Associates of West Broward	Tamarac	Florida
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Regional Medical Oncolgy Center	Wilson	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Aileron Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Bosnia and Herzegovina,  Germany,  Italy,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b Part 2 NSCLC	Proportion of completed treatment cycles that are free of Grade = 3 hematological toxicities (including neutropenia, anemia, thrombocytopenia and febrile neutropenia), and free of chemotherapy dose reductions, and free of use of growth factors and transfusions.	Approximately 6 months
Primary	Phase 1b Part 1 SCLC	Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs)	Approximately 19 months