Ignite Creation Date:
2024-07-17 @ 10:56 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06498648
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-12
First Post:
2024-07-10
Brief Title:
Testing the Addition of an Anti-cancer Drug Abemaciclib to the Usual Chemotherapy Treatment Gemcitabine for Soft Tissue Sarcoma
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Phase III Study to Evaluate the Feasibility and Efficacy of Sequential Abemaciclib and Gemcitabine Treatment in Patients With Retinoblastoma Rb Sarcomas
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
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:
This phase 12 trial tests the side effects and best dose of abemaciclib when added to gemcitabine and compares the effectiveness of that treatment to the usual treatment of gemcitabine with docetaxel for the treatment of patients with soft tissue sarcoma that may have spread from where it first started to nearby tissue lymph nodes or distant parts of the body advanced or that has spread from where it first started primary site to other places in the body metastatic phase 1 or patients with leiomyosarcoma or dedifferentiated liposarcoma phase 2 Abemaciclib is in a class of medications called kinase inhibitors It works by blocking the action of an abnormal protein that signals tumor cells to multiply This helps slow or stop the spread of tumor cells Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells Docetaxel is in a class of medications called taxanes It stops cancer cells from growing and dividing and may kill them Giving abemaciclib with gemcitabine may be safe and effective when compared to treatment with gemcitabine and docetaxel for patients with advanced or metastatic soft tissue sarcoma or leiomyosarcoma or dedifferentiated liposarcoma
Detailed Description:
PRIMARY OBJECTIVES
I The primary objective of the phase 1 part of this trial is to define the schedule of sequential abemaciclib and gemcitabine and recommended phase 2 dose RP2D of retinoblastoma positive Rbve sarcomas
II The primary objective of the phase 2 part of the trial is to define the progression-free survival PFS of sequential abemaciclib followed by gemcitabine at RP2D compared to the standard of care gemcitabine and docetaxel in advanced Rbve leiomyosarcomas and dedifferentiated liposarcomas
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity in phase 1 II To determine cell cycle arrest and recovery with abemaciclib 200mg twice per day BID 5 to 7 days by blood thymidine kinase activity Tka
III To assess the toxicity profile of the sequential abemaciclib followed by gemcitabine treatment using Common Terminology Criteria for Adverse Events CTCAE version 5 in phase 1 phase 2
IV To determine the preliminary objective response rate ORR by Response Criteria in Solid Tumors RECIST11 in phase 1
V To compare overall survival OS of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2
VI To compare the objective response rate ORR at time of best response by RECIST11 of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2
VII To compare PFS and ORR after cross-over in each treatment arm VIII To identify mechanisms of resistance to sequential treatment through correlative studies of the cell cycle genes
EXPLORATORY OBJECTIVE
I To determine cell cycle arrest and recovery with abemaciclib 200mg BID 5 to 7 days by fluorothymidine F-18 18F-FLT positron emission tomography PET and its association with blood Tka
OUTLINE Patients in phase 1 part A are assigned to cohort 1 or 2 Patients in phase 2 are randomized to arm A or arm B and may cross over to the alternate arm after disease progression
PHASE 1 PART A
COHORT I Patients receive abemaciclib orally PO twice per day BID on days 1-5 and 14-18 of each cycle and gemcitabine intravenously IV over 90 minutes on days 8 and 22 of each cycle Cycles repeat every 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity Patients may change to Phase 1 Part B treatment once the recommended schedule is determined Patients also receive 18F-FLT IV and undergo PETcomputed tomography CT during screening and on study Additionally patients undergo blood sample collection during screening and on study as well as possible tumor biopsy during screening
COHORT II Patients receive abemaciclib PO BID on days 1-7 and gemcitabine IV over 90 minutes on day 10 of each cycle Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity Patients may change to Phase 1 Part B treatment once the recommended schedule is determined Patients also receive 18F-FLT IV and undergo PETCT during screening and on study Additionally patients undergo blood sample collection during screening and on study as well as possible tumor biopsy during screening
PHASE 1 PART B Patients receive the selected treatment schedule Cohort 1 or Cohort 2 as above Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity
PHASE 2
ARM A Patients receive abemaciclib PO BID and gemcitabine IV on the schedule determined in phase 1 of the trial Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity At the time of disease progression patients may cross over to arm B Patients undergo blood sample collection throughout the study Patients may also undergo tumor biopsy during screening
ARM B Patients receive gemcitabine IV over 90 minutes on days 1 and 8 of each cycle and docetaxel IV over 60 minutes on day 8 of each cycle Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity At the time of disease progression patients may cross over to arm A Patients undergo blood sample collection throughout the study Patients may also undergo tumor biopsy during screening
After completion of study treatment patients are followed up every 3 months for up to 2 years
I The primary objective of the phase 1 part of this trial is to define the schedule of sequential abemaciclib and gemcitabine and recommended phase 2 dose RP2D of retinoblastoma positive Rbve sarcomas
II The primary objective of the phase 2 part of the trial is to define the progression-free survival PFS of sequential abemaciclib followed by gemcitabine at RP2D compared to the standard of care gemcitabine and docetaxel in advanced Rbve leiomyosarcomas and dedifferentiated liposarcomas
SECONDARY OBJECTIVES
I To observe and record anti-tumor activity in phase 1 II To determine cell cycle arrest and recovery with abemaciclib 200mg twice per day BID 5 to 7 days by blood thymidine kinase activity Tka
III To assess the toxicity profile of the sequential abemaciclib followed by gemcitabine treatment using Common Terminology Criteria for Adverse Events CTCAE version 5 in phase 1 phase 2
IV To determine the preliminary objective response rate ORR by Response Criteria in Solid Tumors RECIST11 in phase 1
V To compare overall survival OS of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2
VI To compare the objective response rate ORR at time of best response by RECIST11 of sequential abemaciclib followed by gemcitabine at RP2D to the standard of care gemcitabine and docetaxel in phase 2
VII To compare PFS and ORR after cross-over in each treatment arm VIII To identify mechanisms of resistance to sequential treatment through correlative studies of the cell cycle genes
EXPLORATORY OBJECTIVE
I To determine cell cycle arrest and recovery with abemaciclib 200mg BID 5 to 7 days by fluorothymidine F-18 18F-FLT positron emission tomography PET and its association with blood Tka
OUTLINE Patients in phase 1 part A are assigned to cohort 1 or 2 Patients in phase 2 are randomized to arm A or arm B and may cross over to the alternate arm after disease progression
PHASE 1 PART A
COHORT I Patients receive abemaciclib orally PO twice per day BID on days 1-5 and 14-18 of each cycle and gemcitabine intravenously IV over 90 minutes on days 8 and 22 of each cycle Cycles repeat every 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity Patients may change to Phase 1 Part B treatment once the recommended schedule is determined Patients also receive 18F-FLT IV and undergo PETcomputed tomography CT during screening and on study Additionally patients undergo blood sample collection during screening and on study as well as possible tumor biopsy during screening
COHORT II Patients receive abemaciclib PO BID on days 1-7 and gemcitabine IV over 90 minutes on day 10 of each cycle Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity Patients may change to Phase 1 Part B treatment once the recommended schedule is determined Patients also receive 18F-FLT IV and undergo PETCT during screening and on study Additionally patients undergo blood sample collection during screening and on study as well as possible tumor biopsy during screening
PHASE 1 PART B Patients receive the selected treatment schedule Cohort 1 or Cohort 2 as above Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity
PHASE 2
ARM A Patients receive abemaciclib PO BID and gemcitabine IV on the schedule determined in phase 1 of the trial Cycles repeat every 21 or 28 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity At the time of disease progression patients may cross over to arm B Patients undergo blood sample collection throughout the study Patients may also undergo tumor biopsy during screening
ARM B Patients receive gemcitabine IV over 90 minutes on days 1 and 8 of each cycle and docetaxel IV over 60 minutes on day 8 of each cycle Cycles repeat every 21 days for up to 2 years of total treatment in the absence of disease progression or unacceptable toxicity At the time of disease progression patients may cross over to arm A Patients undergo blood sample collection throughout the study Patients may also undergo tumor biopsy during screening
After completion of study treatment patients are followed up every 3 months for up to 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2024-05665 | REGISTRY | None | None |
| 10657 | OTHER | None | None |
| 10657 | OTHER | None | None |
| UM1CA186688 | NIH | None | None |