Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT03009201|
Recruitment Status : Recruiting
First Posted : January 4, 2017
Last Update Posted : March 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Angiosarcoma Metastatic Epithelioid Sarcoma Metastatic Fibrosarcoma Metastatic Leiomyosarcoma Metastatic Liposarcoma Metastatic Malignant Peripheral Nerve Sheath Tumor Metastatic Synovial Sarcoma Metastatic Undifferentiated Pleomorphic Sarcoma Myxofibrosarcoma Pleomorphic Rhabdomyosarcoma Stage III Soft Tissue Sarcoma Stage IV Soft Tissue Sarcoma Undifferentiated (Embryonal) Sarcoma||Drug: Doxorubicin Drug: Ribociclib||Phase 1|
This is a dose-escalation study of the CDK4/6 inhibitor ribociclib in combination with standard-dose doxorubicin.
I. To determine the recommended phase 2 dose (RP2D) of ribociclib in combination with doxorubicin in subjects with advanced soft tissue sarcomas.
I. To assess preliminary anti-tumor activity of ribociclib in combination with doxorubicin in subjects with advanced soft tissue sarcomas (Progression-Free Survival and Overall Response Rate).
II. To characterize the safety and tolerability of ribociclib in combination with doxorubicin.
A mandatory biopsy will be obtained after 7 days of ribociclib treatment.
TREATMENT: Patients receive ribociclib orally (PO) daily on days 1-7, and doxorubicin intravenously (IV) on day 10. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After 6 courses, patients may receive maintenance treatment with ribociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
STARTING DOSE COHORT: Ribociclib 400 mg with doxorubicin 75 mg/m2.
FOLLOW-UP: After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for 12 months.
RATIONALE: Over-expression of CDK4 or loss of the CDK4 inhibitor p16 are common in sarcomas and result in a selective growth advantage by bypassing normal cell cycle checkpoints. Intact pRb is required for CDK4/6 inhibition to be effective, therefore all eligible subjects must have documented pRb expression by IHC on archival tissue. Synergy between CDK4 inhibition and chemotherapy has been documented in preclinical models when given sequentially, suggestion a role for cell cycle synchronization.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1B Study of Ribociclib in Combination With Doxorubicin in Advanced Soft Tissue Sarcomas|
|Actual Study Start Date :||March 10, 2017|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Treatment (ribociclib, doxorubicin hydrochloride)
Patients receive ribociclib PO daily on days 1-7, and doxorubicin hydrochloride IV on day 10. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive ribociclib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Incidence of DLTs of adverse events graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 [ Time Frame: up to 21 days ]All adverse events (AEs) will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.
- Incidence of adverse events, SAEs, assessed by NCI CTCAE v 4.03 [ Time Frame: Up to 12 months ]Analyses will be performed for all patients having received at least one dose of study drug. Serious adverse events, and AEs will be summarized using descriptive statistics.
- Incidence of dose modifications (interruptions, reductions, intensity) due to adverse events [ Time Frame: Up to 12 months ]Analyses will be performed for all patients having received at least one dose of study drug. AEs leading to withdrawal/dose interruptions/dose modification will be summarized using descriptive statistics.
- Objective response rate (ORR) defined as the proportion of patients who achieved a complete response or a partial response based on RECIST v1 [ Time Frame: Up to 12 months ]The ORR, along with exact two-sided 95% confidence intervals, will be reported for the study.
- Progression-free survival (PFS) [ Time Frame: From first dose of protocol therapy to time of documented radiographic and/or clinical disease progression or death from any cause, whichever occurs first, assessed up to 12 months ]The Kaplan-Meier product limit method will be used to estimate PFS of the median PFS and PFS rates at clinically relevant time points will be provided with the 90% CI.
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): NCT03009201
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Laura Carter 503-418-9354 firstname.lastname@example.org|
|Contact: Phil Norr 503-494-0825 email@example.com|
|Principal Investigator: Lara E. Davis|
|Principal Investigator:||Lara Davis||OHSU Knight Cancer Institute|