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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04022876 |
|
Recruitment Status :
Terminated
(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)
First Posted : July 17, 2019
Last Update Posted : October 10, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 35 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 |
| Actual Primary Completion Date : | July 30, 2022 |
| Actual Study Completion Date : | August 30, 2022 |
| 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. |
- 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.
- 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)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
Show 28 study locations
| 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: | October 10, 2022 |
| Last Verified: | October 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
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 |