Clinical trial NCT04022876: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Small-cell Lung Cancer
Lead sponsor: Aileron Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 1b Part 2 NSCLC
timeFrame: Approximately 6 months
measure: Phase 1b Part 1 SCLC
timeFrame: Approximately 19 months
Secondary outcomes:
Other outcomes:
Locations:
city: Kingman
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Miami
country: United States
facility: Mount Sinai Cancer Research Program
state: Florida
city: Tamarac
country: United States
facility: Oncology & Hematology Associates of West Broward
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Wilson
country: United States
facility: Regional Medical Oncolgy Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Institute
state: Ohio
city: Portland
country: United States
facility: OSHU CHO Northwest
state: Oregon
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska, Lung Clinic
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Center University of Sarajevo, Oncology Clinic
city: Berlin
country: Germany
facility: Charité Comprehensive Cancer Center Benjamin Franklin Hamato, Onkologische
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg Thoraxklinik Heidelberg
city: Muenchen
country: Germany
facility: LMU Klinikum der Universitaet Muenchen, Respiratory Medicine and Thoracic Oncology, Campus Innenstandt
city: Muenchen
country: Germany
facility: München Klinik Neuperlach, Klinik für Hamatologie und Onkologie, Studienburo Neuperlach/Harlaching
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori, Dino Amadori
city: Modena
country: Italy
facility: Azienda Ospedaliero, Universitaria di Modena, Policlinico di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori di Napoli, IRCCS, Fondazione, G. Pascale
city: Pavia
country: Italy
facility: Università degli Studi di Pavia, IRCCS, Fondazione, Policlinico San Matteo
city: Ravenna
country: Italy
facility: Azienda Unità Sanitaria Locale della Romagna, Ospedale Santa Maria delle Croci
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Poznań
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego
city: Belgrade
country: Serbia
facility: CHC Bezanijska Kosa
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia, Pulmonology Clinic
city: Niš
country: Serbia
facility: Clinical Centre Nis, Clinic for Pulmonary Diseases
city: Novi Sad
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
Study officials:
References: