Back to resultsA Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)
Primary Purpose
Non Small Cell Lung Cancer, Small-cell Lung Cancer
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ALRN-6924
Carboplatin
Pemetrexed
Placebo
ALRN-6924
Topotecan
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer
Eligibility Criteria
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.
Sites / Locations
- Arizona Cancer Center
- Mount Sinai Cancer Research Program
- Oncology & Hematology Associates of West Broward
- H. Lee Moffitt Cancer Center & Research Institute
- Regional Medical Oncolgy Center
- Gabrail Cancer Institute
- OSHU CHO Northwest
- Gettysburg Cancer Center
- University Clinical Center of the Republic of Srpska, Lung Clinic
- Clinical Center University of Sarajevo, Oncology Clinic
- Charité Comprehensive Cancer Center Benjamin Franklin Hamato, Onkologische
- Universitaetsklinikum Heidelberg Thoraxklinik Heidelberg
- LMU Klinikum der Universitaet Muenchen, Respiratory Medicine and Thoracic Oncology, Campus Innenstandt
- München Klinik Neuperlach, Klinik für Hamatologie und Onkologie, Studienburo Neuperlach/Harlaching
- Istituto Romagnolo per lo Studio dei Tumori, Dino Amadori
- Azienda Ospedaliero, Universitaria di Modena, Policlinico di Modena
- Istituto Nazionale Tumori di Napoli, IRCCS, Fondazione, G. Pascale
- Università degli Studi di Pavia, IRCCS, Fondazione, Policlinico San Matteo
- Azienda Unità Sanitaria Locale della Romagna, Ospedale Santa Maria delle Croci
- Azienda Ospedaliera Universitaria Integrata Verona
- Szpital Kliniczny Przemienienia Panskiego
- CHC Bezanijska Kosa
- University Clinical Centre of Serbia, Pulmonology Clinic
- Clinical Centre Nis, Clinic for Pulmonary Diseases
- Institute for Pulmonary Diseases of Vojvodina
- Hospital Clinico San Carlos
- Hospital Universitario 12 de Octubre
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 2 NSCLC: ALRN-6924+Carboplatin+Pemetrexed
Part 2 NSCLC: Placebo+Carboplatin+Pemetrexed
Part 1 SCLC: ALRN-6924+Topotecan
Arm Description
Outcomes
Primary Outcome Measures
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.
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)
Secondary Outcome Measures
Full Information
NCT ID
NCT04022876
First Posted
July 12, 2019
Last Updated
October 7, 2022
Sponsor
Aileron Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04022876
Brief Title
A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)
Official Title
A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
With a favorable safety profile the difference between treatment groups for the primary composite endpoint was not sufficient to generate statistically significant results with the targeted sample size
Study Start Date
September 3, 2019 (Actual)
Primary Completion Date
July 30, 2022 (Actual)
Study Completion Date
August 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aileron Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Small-cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 2 NSCLC: ALRN-6924+Carboplatin+Pemetrexed
Arm Type
Experimental
Arm Title
Part 2 NSCLC: Placebo+Carboplatin+Pemetrexed
Arm Type
Experimental
Arm Title
Part 1 SCLC: ALRN-6924+Topotecan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ALRN-6924
Intervention Description
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
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin administered IV on Day 1 of every 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
Pemetrexed administered IV on Day 1 of every 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Intervention Name(s)
ALRN-6924
Intervention Description
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
Intervention Name(s)
Topotecan
Intervention Description
Topotecan administered IV on Days 1-5 of every 21-day cycle.
Primary Outcome Measure Information:
Title
Phase 1b Part 2 NSCLC
Description
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.
Time Frame
Approximately 6 months
Title
Phase 1b Part 1 SCLC
Description
Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs)
Time Frame
Approximately 19 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Arizona Cancer Center
City
Kingman
State/Province
Arizona
ZIP/Postal Code
86409
Country
United States
Facility Name
Mount Sinai Cancer Research Program
City
Miami
State/Province
Florida
ZIP/Postal Code
33140
Country
United States
Facility Name
Oncology & Hematology Associates of West Broward
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Regional Medical Oncolgy Center
City
Wilson
State/Province
North Carolina
ZIP/Postal Code
27893
Country
United States
Facility Name
Gabrail Cancer Institute
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
OSHU CHO Northwest
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Gettysburg Cancer Center
City
Gettysburg
State/Province
Pennsylvania
ZIP/Postal Code
17325
Country
United States
Facility Name
University Clinical Center of the Republic of Srpska, Lung Clinic
City
Banja Luka
Country
Bosnia and Herzegovina
Facility Name
Clinical Center University of Sarajevo, Oncology Clinic
City
Sarajevo
Country
Bosnia and Herzegovina
Facility Name
Charité Comprehensive Cancer Center Benjamin Franklin Hamato, Onkologische
City
Berlin
Country
Germany
Facility Name
Universitaetsklinikum Heidelberg Thoraxklinik Heidelberg
City
Heidelberg
Country
Germany
Facility Name
LMU Klinikum der Universitaet Muenchen, Respiratory Medicine and Thoracic Oncology, Campus Innenstandt
City
Muenchen
Country
Germany
Facility Name
München Klinik Neuperlach, Klinik für Hamatologie und Onkologie, Studienburo Neuperlach/Harlaching
City
Muenchen
Country
Germany
Facility Name
Istituto Romagnolo per lo Studio dei Tumori, Dino Amadori
City
Meldola
Country
Italy
Facility Name
Azienda Ospedaliero, Universitaria di Modena, Policlinico di Modena
City
Modena
Country
Italy
Facility Name
Istituto Nazionale Tumori di Napoli, IRCCS, Fondazione, G. Pascale
City
Napoli
Country
Italy
Facility Name
Università degli Studi di Pavia, IRCCS, Fondazione, Policlinico San Matteo
City
Pavia
Country
Italy
Facility Name
Azienda Unità Sanitaria Locale della Romagna, Ospedale Santa Maria delle Croci
City
Ravenna
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Integrata Verona
City
Verona
Country
Italy
Facility Name
Szpital Kliniczny Przemienienia Panskiego
City
Poznań
Country
Poland
Facility Name
CHC Bezanijska Kosa
City
Belgrade
Country
Serbia
Facility Name
University Clinical Centre of Serbia, Pulmonology Clinic
City
Belgrade
Country
Serbia
Facility Name
Clinical Centre Nis, Clinic for Pulmonary Diseases
City
Niš
Country
Serbia
Facility Name
Institute for Pulmonary Diseases of Vojvodina
City
Novi Sad
Country
Serbia
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
MD Anderson Cancer Center
City
Madrid
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)
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