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出境医 / 临床实验 / A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Myelosuppression
A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Myelosuppression
Study Description
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 |
|---|---|---|
| Non Small Cell Lung Cancer | Drug: ALRN-6924 Drug: Carboplatin Drug: Pemetrexed Other: Placebo | 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.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Supportive Care |
| Official Title: | A Phase 1b/2 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 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Phase 1b Part 2
ALRN-6924 will be administered IV on days 0-2 of every 21-day cycle Carboplatin and pemetrexed will be administered IV after ALRN-6924 on day 1 of every 21-day cycle |
Drug: ALRN-6924
ALRN-6924 will be administered IV on days 0-2 of every 21-day treatment cycle Placebo will be administered IV on days 0-2 of every 21-day treatment cycle Drug: Carboplatin Carboplatin will be administered IV on day 1 of every 21-day treatment cycle
Drug: Pemetrexed Pemetrexed will be administered on day 1 of every 21-day treatment cycle
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Experimental: Phase 1b Control
Placebo will be administered IV on days 0-2 of every 21-day cycle Carboplatin and pemetrexed will be administered IV after ALRN-6924 on day 1 of every 21-day cycle |
Drug: Carboplatin
Carboplatin will be administered IV on day 1 of every 21-day treatment cycle
Drug: Pemetrexed Pemetrexed will be administered on day 1 of every 21-day treatment cycle
Other: Placebo Placebo will be administered IV on days 0-2 of every 21-day treatment cycle
|
Outcome Measures
Primary Outcome Measures :
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of patients with Grade ≥ 3 neutropenia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of patients with Grade ≥ 3 thrombocytopenia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of patients with Grade ≥ 3 anemia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of patients with Grade 4 neutropenia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of patients with febrile neutropenia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Duration of Grade 4 neutropenia
- Part 2: Evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 6 months ]Proportion of completed treatment cycles without chemotherapy dose reduction or without the use of growth factors or transfusions
Secondary Outcome Measures :
- Part 2: Evaluate the safety and tolerability of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC adenocarcinoma histology receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Approximately 7 months ]Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs)
- Part 2: Evaluate efficacy of carboplatin plus pemetrexed with or without immunotherapy administered as 1st-line treatment for patients with TP53-mutated advanced NSCLC of adenocarcinoma histology 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.)
- Part 2: Evaluate efficacy of carboplatin plus pemetrexed with or without immunotherapy administered as 1st-line treatment for patients with TP53-mutated advanced NSCLC of adenocarcinoma histology who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 12 months ]Progression free survival hazard ratio (PFS HR)
- Part 2: Evaluate efficacy of carboplatin plus pemetrexed with or without immunotherapy administered as 1st-line treatment for patients with TP53-mutated advanced NSCLC of adenocarcinoma histology who are receiving supportive treatment with ALRN-6924 [ Time Frame: Approximately 18 months ]Overall survival hazard ratio (OS HR)
- Part 2: Further evaluate the PK profile of ALRN-6924 when administered with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Cycle 1 (21 days) ]Peak Plasma Concentration (Cmax)
- Part 2: Further evaluate the PK profile of ALRN-6924 when administered with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Cycle 1 (21 days) ]Area under the plasma concentration versus time curve (AUC)
- Part 2: Further evaluate the PK profile of ALRN-6924 when administered with carboplatin plus pemetrexed with or without immunotherapy [ Time Frame: Cycle 1 (21 days) ]Time of peak plasma concentration (Tmax)
- Part 2: Assess the effect of ALRN-6924 on quality of life in patients receiving 1st-line treatment with carboplatin plus pemetrexed with or without immunotherapy for advanced NSCLC [ Time Frame: Approximately 12 months ]Completion of EORTC Lung Cancer Questionnaire QLQ-LC13
Eligibility Criteria
| 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
Contacts and Locations
Locations
| United States, Ohio | |
| Gabrail Cancer Center | |
| Canton, Ohio, United States, 44718 | |
| Bosnia and Herzegovina | |
| 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 | |
| Poland | |
| Szpital Kliniczny Przemienienia Panskiego | |
| Poznań, Poland | |
| Serbia | |
| CHC Bezanijska kosa | |
| Belgrade, Serbia | |
| Clinical Centre Nis, Clinic for Pulmonary Diseases | |
| Niš, Serbia | |
| Institute for Pulmonary Diseases of Vojvodina | |
| Novi Sad, Serbia | |
| Spain | |
| Hospital Universitario 12 de Octubre | |
| Madrid, Spain | |
Sponsors and Collaborators
Aileron Therapeutics
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | July 12, 2019 | ||||
| First Posted Date ICMJE | July 17, 2019 | ||||
| Last Update Posted Date | May 18, 2021 | ||||
| Actual Study Start Date ICMJE | September 3, 2019 | ||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
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| Original Primary Outcome Measures ICMJE |
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| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Myelosuppression | ||||
| Official Title ICMJE | A Phase 1b/2 Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression | ||||
| 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. | ||||
| 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 ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 1 Phase 2 |
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| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Supportive Care |
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| Condition ICMJE | Non Small Cell Lung Cancer | ||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Active, not recruiting | ||||
| Estimated Enrollment ICMJE |
60 | ||||
| Original Estimated Enrollment ICMJE |
120 | ||||
| Estimated Study Completion Date ICMJE | November 2022 | ||||
| Estimated Primary Completion Date | June 2022 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | Bosnia and Herzegovina, Poland, Serbia, Spain, United States | ||||
| Removed Location Countries | Croatia | ||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT04022876 | ||||
| Other Study ID Numbers ICMJE | ALRN-6924-1-03 | ||||
| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | Aileron Therapeutics | ||||
| Study Sponsor ICMJE | Aileron Therapeutics | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE | Not Provided | ||||
| PRS Account | Aileron Therapeutics | ||||
| Verification Date | May 2021 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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