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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04022876
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics, Inc.

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.


Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Small-cell Lung Cancer Drug: ALRN-6924 Drug: Carboplatin Drug: Pemetrexed Drug: Placebo Drug: Topotecan Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression
Actual Study Start Date : September 3, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 2 NSCLC: ALRN-6924+Carboplatin+Pemetrexed 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.

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

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

Experimental: Part 2 NSCLC: Placebo+Carboplatin+Pemetrexed Drug: Carboplatin
Carboplatin administered IV on Day 1 of every 21-day cycle.

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

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

Experimental: Part 1 SCLC: ALRN-6924+Topotecan 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.

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




Primary Outcome Measures :
  1. Phase 1b Part 2 NSCLC [ Time Frame: Approximately 6 months ]
    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.

  2. Phase 1b Part 1 SCLC [ Time Frame: Approximately 19 months ]
    Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04022876


Locations
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United States, Michigan
Revive Research Institute Inc. Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Adil Akhtar, MD    248-721-9539    aakhtar@rev-research.com   
Revive Research Institute Inc. Recruiting
Farmington Hills, Michigan, United States, 48334
Contact: Savitha Balaraman, MD    248-564-1485    sbalaraman@rev-research.com   
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Nashat Y Gabrail, MD    330-492-3345 ext 209    ngabrailmd@gabrailcancercenter.com   
Bosnia and Herzegovina
University Clinical Center of the Republic of Srpska, Lung Clinic Recruiting
Banja Luka, Bosnia and Herzegovina
Contact: Mirko Turic, MD    +387 51 343 289    mirko.turic@gmail.com   
Clinical Center University of Sarajevo, Clinic for Lung Disease Not yet recruiting
Sarajevo, Bosnia and Herzegovina
Contact: Bakir Mehic, MD    +387 33 297 825    bakir.mehic@kcus.ba   
Clinical Center University of Sarajevo, Oncology Clinic Not yet recruiting
Sarajevo, Bosnia and Herzegovina
Contact: Timur Ceric, MD    +387 33 298 054      
Poland
Szpital Kliniczny Przemienienia Panskiego Recruiting
Poznań, Poland
Contact: Rodryg Ramlau, MD    +48 616 561 700    rramlau@gmail.com   
Serbia
CHC Bezanijska Kosa Not yet recruiting
Belgrade, Serbia
Contact: Zoran Andric, MD    +381 214 805 277      
University Clinical Centre of Serbia, Pulmonology Clinic Not yet recruiting
Belgrade, Serbia
Contact: Milica Kontic, MD    +381 63 554 963      
Clinical Centre Nis, Clinic for Pulmonary Diseases Not yet recruiting
Niš, Serbia
Contact: Milan Rancic, MD    +381 18 200 424      
Institute for Pulmonary Diseases of Vojvodina Not yet recruiting
Novi Sad, Serbia
Contact: Bojan Zaric, MD    +381 214 805 224      
Spain
Hospital Clinico San Carlos Active, not recruiting
Madrid, Spain
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Santiago Ponce, MD    +34 91 469 2313    sponceaix@gmail.com   
MD Anderson Cancer Center Active, not recruiting
Madrid, Spain
Sponsors and Collaborators
Aileron Therapeutics, Inc.
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Responsible Party: Aileron Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04022876    
Other Study ID Numbers: ALRN-6924-1-03
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: July 1, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Carboplatin
Pemetrexed
Topotecan
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Topoisomerase I Inhibitors
Topoisomerase Inhibitors