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A Study of ALRN-6924 for the Prevention of Topotecan-induced Myelosuppression During Treatment for Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT04022876
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Aileron Therapeutics

Brief Summary:
This is a Phase 1b/2, open label, multicenter study of ALRN-6924 for the mitigation or reduction of topotecan-induced myelosuppression during 2nd-line treatment for ED SCLC harboring TP53 mutations.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Drug: ALRN-6924 Drug: Topotecan Phase 1 Phase 2

Detailed Description:

During the Phase 1b portion of the study, 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 Phase 1b.

If pre-determined criteria for safety and myelopreservation activity are met and the RP2D is identified, the Phase 2 portion of the study will be triggered. In Phase 2, patients with ED SCLC requiring 2nd line treatment with topotecan will be randomized 1:1 to either receive topotecan alone or topotecan with supportive ALRN-6924 treatment.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase 1b/2 Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Topotecan-induced Myelosuppression During Treatment for Small Cell Lung Cancer
Actual Study Start Date : September 3, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Phase 1b

ALRN-6924 will be administered IV on days 0-4 of every 21-day cycle

Topotecan will be administered IV after ALRN-6924 on days 1-5 of every 21-day cycle

Drug: ALRN-6924
ALRN-6924 will be administered IV on days 0-4 of every 21-day treatment cycle

Drug: Topotecan
Topotecan will be administered IV on days 1-5 of every 21-day treatment cycle

Experimental: Phase 2 Experimental

ALRN-6924 will be administered IV on days 0-4 of every 21-day cycle

Topotecan will be administered IV after ALRN-6924 on days 1-5 of every 21-day cycle

Drug: ALRN-6924
ALRN-6924 will be administered IV on days 0-4 of every 21-day treatment cycle

Drug: Topotecan
Topotecan will be administered IV on days 1-5 of every 21-day treatment cycle

Experimental: Phase 2 Control
Topotecan will be administered IV on days 1-5 of every 21-day cycle
Drug: Topotecan
Topotecan will be administered IV on days 1-5 of every 21-day treatment cycle




Primary Outcome Measures :
  1. Phase 1b: Evaluate safety and tolerability and determine recommended Phase 2 dose (RP2D) of ALRN-6924 when administered to patients with TP53 mutated extensive disease (ED) small cell lung cancer (SCLC) receiving topotecan as 2nd line treatment [ 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)

  2. Phase 2: Evaluate the myelopreservation effects of ALRN-6924 when administered at the RP2D to patients with TP-53 mutated ED SCLC undergoing 2nd-line treatment with topotecan [ Time Frame: Approximately 12 months ]
    Proportion of patients with Grade ≥ 3 neutropenia


Secondary Outcome Measures :
  1. Phase 1b: Evaluate the myelosuppressive effects of ALRN-6924 when administered to patients with TP53 mutated ED SCLC undergoing 2nd-line treatment with topotecan [ Time Frame: Approximately 7 months ]
    Proportion of patients with Grade ≥ 3 neutropenia

  2. Phase 1b: Evaluate the myelosuppressive effects of ALRN-6924 when administered to patients with TP53 mutated ED SCLC undergoing 2nd-line treatment with topotecan [ Time Frame: Approximately 7 months ]
    Onset to first incidence of Grade ≥ 3 neutropenia

  3. Phase 1b: Evaluate the myelosuppressive effects of ALRN-6924 when administered to patients with TP53 mutated ED SCLC undergoing 2nd-line treatment with topotecan [ Time Frame: Approximately 7 months ]
    Proportion of patients with Grade ≥ 3 thrombocytopenia

  4. Phase 1b: Evaluate the myelosuppressive effects of ALRN-6924 when administered to patients with TP53 mutated ED SCLC undergoing 2nd-line treatment with topotecan [ Time Frame: Approximately 7 months ]
    Proportion of patients with febrile neutropenia

  5. Phase 1b: Evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP-53 mutated ED SCLS who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 7 months ]
    Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  6. Phase 1b: Evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP-53 mutated ED SCLS who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 7 months ]
    Median progression free survival (PFS)

  7. Phase 1b: Evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP-53 mutated ED SCLS who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 7 months ]
    Median overall survival (OS)

  8. Phase 1b: Evaluate the pharmacokinetic (PK) profile of ALRN-6924 when administered with topotecan [ Time Frame: ycle 1 (28 days) ]
    Peak Plasma Concentration (Cmax)

  9. Phase 1b: Evaluate the pharmacokinetic (PK) profile of ALRN-6924 when administered with topotecan [ Time Frame: Cycle 1 (28 days) ]
    Area under the plasma concentration versus time curve (AUC)

  10. Phase 1b: Evaluate the pharmacokinetic (PK) profile of ALRN-6924 when administered with topotecan [ Time Frame: Cycle 1 (28 days) ]
    Time of peak plasma concentration (Tmax)

  11. Phase 2: Further evaluate the safety and tolerability of ALRN-6924 as supportive care during treatment with topotecan [ Time Frame: From the first dose up to 30 days after last dose ]
    Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs)

  12. Phase 2: Further evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP53-mutated ED SCLC who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 12 months ]
    Overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

  13. Phase 2: Further evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP53-mutated ED SCLC who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 12 months ]
    Progression free survival hazard ratio (PFS HR)

  14. Phase 2: Further evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP53-mutated ED SCLC who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 12 months ]
    Overall survival hazard ratio (OS HR)

  15. Phase 2: Further evaluate the PK profile of ALRN-6924 when administered with topotecan [ Time Frame: Cycle 1 (28 days) ]
    Peak Plasma Concentration (Cmax)

  16. Phase 2: Further evaluate the PK profile of ALRN-6924 when administered with topotecan [ Time Frame: Cycle 1 (28 days) ]
    Area under the plasma concentration versus time curve (AUC)

  17. Phase 2: Further evaluate the PK profile of ALRN-6924 when administered with topotecan [ Time Frame: Cycle 1 (28 days) ]
    Time of peak plasma concentration (Tmax)



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

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
  • Mutated TP53: no wild-type (WT) TP53 gene copies within the tumor (i.e., biallelic mutation, biallelic deletion or mutation/deletion), as assessed by next generation sequencing (NGS)
  • 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:

  • 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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Bosnia and Herzegovina
University Clinical Center of the REpublic of Srpska, Lung Clinic Recruiting
Banja Luka, Bosnia and Herzegovina
Contact: Mirko Teric, MD    +387 33 298 054      
Clinical Center University of Sarajevo, ONcology Clinic Recruiting
Sarajevo, Bosnia and Herzegovina
Contact: Timur Ceric, MD    +387 33 298 054      
Poland
Specialist Hospuital of Ludwik Rydygier Sp. z o. o. Not yet recruiting
Kraków, Poland
Szpital Kliniczny Przemienienia Panskiego Not yet recruiting
Poznań, Poland
Centrum Terapii Wspolczesnej Not yet recruiting
Łódź, Poland
Serbia
CHC Bezanijska kosa Recruiting
Belgrade, Serbia
Contact: Zoran Andric, MD    +381 113 010 787      
Clinical Centre Nis, Clinic for Pulmonary Diseases Recruiting
Niš, Serbia
Contact: Milan Rancic, MD    +381 18 200 424      
Institute for Pulmonary Diseases of Vojvodina Recruiting
Novi Sad, Serbia
Contact: Bojan Zaric, MD    +381 214 805 224      
Spain
Hospital Universitario 12 de Octubre Not yet recruiting
Madrid, Spain
Sponsors and Collaborators
Aileron Therapeutics

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Responsible Party: Aileron Therapeutics
ClinicalTrials.gov Identifier: NCT04022876     History of Changes
Other Study ID Numbers: ALRN-6924-1-03
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

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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
Topotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents