NCT03009201

Brief Summary

This phase Ib trial studies the side effects and best dose of ribociclib when giving together with doxorubicin hydrochloride in treating patients with soft tissue sarcomas that has spread to other places or that cannot be removed by surgery (advanced). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ribociclib and doxorubicin hydrochloride may work better in treating patients with soft tissue sarcoma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2017

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 5, 2016

Completed
1 month until next milestone

First Posted

Study publicly available on registry

January 4, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

March 10, 2017

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 8, 2019

Completed
3.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2023

Completed
Last Updated

August 16, 2023

Status Verified

August 1, 2023

Enrollment Period

2.6 years

First QC Date

December 5, 2016

Last Update Submit

August 14, 2023

Conditions

Advanced Soft Tissue SarcomaLocally Advanced AngiosarcomaLocally Advanced LeiomyosarcomaLocally Advanced LiposarcomaLocally Advanced Malignant Peripheral Nerve Sheath TumorLocally Advanced MyxofibrosarcomaLocally Advanced Undifferentiated Pleomorphic SarcomaMetastatic AngiosarcomaMetastatic Epithelioid SarcomaMetastatic FibrosarcomaMetastatic LiposarcomaMetastatic Malignant Peripheral Nerve Sheath TumorMetastatic MyxofibrosarcomaMetastatic Soft Tissue SarcomaMetastatic Synovial SarcomaMetastatic Undifferentiated Pleomorphic SarcomaMyxofibrosarcomaPleomorphic RhabdomyosarcomaStage III Soft Tissue Sarcoma AJCC v7Stage IV Soft Tissue Sarcoma AJCC v7Undifferentiated (Embryonal) SarcomaUnresectable LeiomyosarcomaUnresectable LiposarcomaUnresectable Malignant Peripheral Nerve Sheath TumorUnresectable Soft Tissue SarcomaUnresectable Synovial SarcomaUnresectable Undifferentiated Pleomorphic Sarcoma

Outcome Measures

Primary Outcomes (1)

  • Incidence of dose limiting toxicities (DLTs) of adverse events

    Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. 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.

    Up to 21 days

Secondary Outcomes (4)

  • Progression-free survival (PFS)

    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

  • Objective response rate (ORR)

    Up to 12 months

  • Incidence of adverse events, SAEs

    Up to 12 months

  • Incidence of dose modifications (interruptions, reductions, intensity) due to adverse events

    Up to 12 months

Study Arms (1)

Treatment (ribociclib, doxorubicin hydrochloride)

EXPERIMENTAL

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 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive ribociclib PO daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Doxorubicin HydrochlorideOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyDrug: Ribociclib

Interventions

Doxorubicin HydrochlorideDRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex
Treatment (ribociclib, doxorubicin hydrochloride)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (ribociclib, doxorubicin hydrochloride)
Pharmacological StudyOTHER

Correlative studies

Treatment (ribociclib, doxorubicin hydrochloride)
RibociclibDRUG

Given PO

Also known as: Kisqali, LEE-011, LEE011
Treatment (ribociclib, doxorubicin hydrochloride)

Eligibility Criteria

Age12 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Pathologically confirmed diagnosis of intermediate or high-grade soft tissue sarcoma for which single-agent doxorubicin is appropriate therapy, including but not limited to:
  • Synovial sarcoma
  • Fibrosarcoma
  • Undifferentiated sarcoma
  • Liposarcoma
  • Leiomyosarcoma
  • Angiosarcoma
  • Malignant peripheral nerve sheath tumor
  • Pleomorphic rhabdomyosarcoma
  • Myxofibrosarcoma
  • Epithelioid sarcoma
  • Undifferentiated pleomorphic sarcoma
  • Locally advanced unresectable or metastatic disease with no standard curative therapy available
  • Archival tumor tissue retinoblastoma-associated protein (pRb) positive by immunohistochemistry (IHC)
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • +17 more criteria

You may not qualify if:

  • All prior treatment-related toxicities resolved to =\< grade 1 or are determined to be clinically stable by the investigator
  • Has completed prior therapies according to the criteria below:
  • Cytotoxic chemotherapy - at least 21 days since last dose prior to first dose of ribociclib
  • Small molecule inhibitors - at least 14 days since last dose prior to first dose of ribociclib
  • Monoclonal antibodies - at least 3 half-lives since last dose prior to first dose of ribociclib; exception: denosumab for bony metastases is allowable
  • Immunotherapy (e.g. tumor vaccines) - at least 42 days since last dose prior to first dose of ribociclib
  • Radiation - at least 14 days since last dose prior to first dose of ribociclib
  • Able to swallow capsules
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
  • Life expectancy \> 3 months
  • Ability to understand and the willingness to sign a written informed consent document; subject has signed the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements
  • Subjects with low grade tumors (histologic grade 1/3)
  • Histologic diagnosis for which single-agent doxorubicin is NOT appropriate therapy, including but not limited to:
  • Alveolar or embryonal rhabdomyosarcoma
  • Ewings sarcoma or primitive neuroectodermal tumor (PNET)
  • +30 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

HemangiosarcomaSarcomaFibrosarcomaLiposarcomaNeurofibrosarcomaDermatofibrosarcomaSarcoma, SynovialHistiocytoma, Malignant FibrousDisorders of Sex Development

Interventions

Doxorubicinribociclib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Vascular TissueNeoplasms, Fibrous TissueNeoplasms, Connective TissueNeoplasms, Adipose TissueNeurofibromaNerve Sheath NeoplasmsNeoplasms, Nerve TissuePeripheral Nervous System NeoplasmsNervous System NeoplasmsNervous System DiseasesPeripheral Nervous System DiseasesNeuromuscular DiseasesHistiocytomaUrogenital AbnormalitiesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

DaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydrates

Study Officials

  • Lara E Davis

    OHSU Knight Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

December 5, 2016

First Posted

January 4, 2017

Study Start

March 10, 2017

Primary Completion

October 8, 2019

Study Completion

June 30, 2023

Last Updated

August 16, 2023

Record last verified: 2023-08

Locations

US(1)