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

NCT ID: NCT04022876

Last Updated: 2022-10-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-03
• Study Completion Date: 2022-08-30

Brief 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.

Detailed 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.

Conditions

Non Small Cell Lung Cancer; Small-cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 2 NSCLC: ALRN-6924+Carboplatin+Pemetrexed

Group Type: EXPERIMENTAL

ALRN-6924

Intervention Type: DRUG

ALRN-6924 administered IV on Days 0-2 prior to carboplatin and pemetrexed administered IV on Day 1 of every 21-day cycle.

Carboplatin

Intervention Type: DRUG

Carboplatin administered IV on Day 1 of every 21-day cycle.

Pemetrexed

Intervention Type: DRUG

Pemetrexed administered IV on Day 1 of every 21-day cycle.

Part 2 NSCLC: Placebo+Carboplatin+Pemetrexed

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

Carboplatin administered IV on Day 1 of every 21-day cycle.

Pemetrexed

Intervention Type: DRUG

Pemetrexed administered IV on Day 1 of every 21-day cycle.

Placebo

Intervention Type: DRUG

Placebo administered IV on Days 0-2 prior to carboplatin and pemetrexed administered IV on Day 1 of every 21-day cycle.

Part 1 SCLC: ALRN-6924+Topotecan

Group Type: EXPERIMENTAL

ALRN-6924

Intervention Type: DRUG

ALRN-6924 administered IV on Days 0-4 prior to topotecan administered IV on Days 1-5 of every 21-day cycle.

Topotecan

Intervention Type: DRUG

Topotecan administered IV on Days 1-5 of every 21-day cycle.

Interventions

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.

Intervention Type: DRUG

Carboplatin

Carboplatin administered IV on Day 1 of every 21-day cycle.

Intervention Type: DRUG

Pemetrexed

Pemetrexed administered IV on Day 1 of every 21-day cycle.

Intervention Type: DRUG

Placebo

Placebo administered IV on Days 0-2 prior to carboplatin and pemetrexed administered IV on Day 1 of every 21-day cycle.

Intervention Type: DRUG

ALRN-6924

ALRN-6924 administered IV on Days 0-4 prior to topotecan administered IV on Days 1-5 of every 21-day cycle.

Intervention Type: DRUG

Topotecan

Topotecan administered IV on Days 1-5 of every 21-day cycle.

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aileron Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Cancer Center

Kingman, Arizona, United States

Mount Sinai Cancer Research Program

Miami, Florida, 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, United States

Gabrail Cancer Institute

Canton, Ohio, United States

OSHU CHO Northwest

Portland, Oregon, United States

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States

University Clinical Center of the Republic of Srpska, Lung Clinic

Banja Luka, , Bosnia and Herzegovina

Clinical Center University of Sarajevo, Oncology Clinic

Sarajevo, , Bosnia and Herzegovina

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

München, , Germany

München Klinik Neuperlach, Klinik für Hamatologie und Onkologie, Studienburo Neuperlach/Harlaching

München, , Germany

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, , Italy

Szpital Kliniczny Przemienienia Panskiego

Poznan, , Poland

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, , Serbia

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

MD Anderson Cancer Center

Madrid, , Spain

Countries

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

Other Identifiers

ALRN-6924-1-03

Identifier Type: -

Identifier Source: org_study_id