Ignite Creation Date:
2024-05-06 @ 3:19 PM
Last Modification Date:
2024-10-26 @ 1:47 PM
Study NCT ID:
NCT04594005
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-10-06
First Post:
2020-10-14
Brief Title:
CDK46 Tumor Abemaciclib Paclitaxel
Sponsor:
Yonsei University
Organization:
Yonsei University
Study Overview
Official Title:
An Open-label Multi-center Phase IBII Study of Abemaciclib With Paclitaxel for CDK46 Pathway Activated Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cyclin D-dependent kinases CDKs are often activated in human cancer owing to various genetic and epigenetic events This affects regulatory pathways and it results in uncontrolled proliferation due to loss of checkpoint integrity Most tumors show increased activity of CDKs and this permits escape from senescence during the evolution of malignancy
Among them cyclin D-CDK46-INK4 pathway alterations accelerate G1 progression which provides proliferative and survival advantage to cancer Therefore preclinical data demonstrated inhibition of cyclin D-dependent kinase activity have therapeutic benefit CDK46 controls entry into cell cycle progression by regulating Retinoblastoma protein Rb The majority of human cancers are known to retain wild-type Rb In addition CDK4 amplification and mutations also noted in several tumors In Rb retained tumors CDK 46 inhibitors reduced Rb phosphorylation and induced G1 arrest In previous study CDK46 inhibitor showed antitumor activities in Rb-positive breast and colon cancer cell lines Rapid tumor regression was also noticed in mouse xenograft model In CDK4 amplified sarcoma cell lines knockdown of CDK4 inhibited cancer cell proliferation
Cyclin D1 acts with CDK4 and CDK6 to phosphorylate Rb and promote cell-cycle progression and CDK46 inhibitor might be effective for the patients with CCND123 amplificationmutation or CDK 46 amplification Therefore basket trial NCT03310879 is ongoing for the patients with genomic alterations in CCND1 CDKN2A or CDK4 Amplificationmutation of CCND123 and CDK46 occurs in approximately 15-30 of various solid tumors sarcoma GBM melanoma gem cell tumor and gynecologic tumors Regarding the more potent synergistic effect paclitaxel demonstrated a rationale for promising combination partner with CDK 46 inhibitors In non-small cell lung cancer cell lines synergistic anti-tumor activities were reported with paclitaxel combination Corollary we planned to conduct the phase IbII trial of abemaciclib and paclitaxel combination in CDK46 pathway activated tumors as one subgroup of multi-arms in ongoing basket trial
Among them cyclin D-CDK46-INK4 pathway alterations accelerate G1 progression which provides proliferative and survival advantage to cancer Therefore preclinical data demonstrated inhibition of cyclin D-dependent kinase activity have therapeutic benefit CDK46 controls entry into cell cycle progression by regulating Retinoblastoma protein Rb The majority of human cancers are known to retain wild-type Rb In addition CDK4 amplification and mutations also noted in several tumors In Rb retained tumors CDK 46 inhibitors reduced Rb phosphorylation and induced G1 arrest In previous study CDK46 inhibitor showed antitumor activities in Rb-positive breast and colon cancer cell lines Rapid tumor regression was also noticed in mouse xenograft model In CDK4 amplified sarcoma cell lines knockdown of CDK4 inhibited cancer cell proliferation
Cyclin D1 acts with CDK4 and CDK6 to phosphorylate Rb and promote cell-cycle progression and CDK46 inhibitor might be effective for the patients with CCND123 amplificationmutation or CDK 46 amplification Therefore basket trial NCT03310879 is ongoing for the patients with genomic alterations in CCND1 CDKN2A or CDK4 Amplificationmutation of CCND123 and CDK46 occurs in approximately 15-30 of various solid tumors sarcoma GBM melanoma gem cell tumor and gynecologic tumors Regarding the more potent synergistic effect paclitaxel demonstrated a rationale for promising combination partner with CDK 46 inhibitors In non-small cell lung cancer cell lines synergistic anti-tumor activities were reported with paclitaxel combination Corollary we planned to conduct the phase IbII trial of abemaciclib and paclitaxel combination in CDK46 pathway activated tumors as one subgroup of multi-arms in ongoing basket trial
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None