NCT04145700

Brief Summary

This study is being conducted to test the safety and efficacy of ramucirumab in combination with other chemotherapy in the treatment of relapsed, recurrent, or refractory synovial sarcoma (SS) in children and young adults. This trial is part of the CAMPFIRE master protocol (NCT05999994) which is a platform to accelerate the development of new treatments for pediatric and young adult participants with cancer. Your participation in this trial could last 12 months or longer, depending on how you and your tumor respond.

Trial Health

68
Monitor

Trial Health Score

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

Enrollment
23

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2020

Typical duration for phase_1

Geographic Reach
10 countries

56 active sites

Status
terminated

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

October 29, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 31, 2019

Completed
4 months until next milestone

Study Start

First participant enrolled

March 4, 2020

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 23, 2023

Completed
7 months until next milestone

Results Posted

Study results publicly available

September 13, 2023

Completed
Last Updated

September 13, 2023

Status Verified

August 1, 2023

Enrollment Period

3 years

First QC Date

October 29, 2019

Results QC Date

August 23, 2023

Last Update Submit

August 23, 2023

Conditions

Keywords

soft tissue sarcomaadolescents and young adults (AYAs)adolescent

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS)

    PFS is defined as the time from randomization until the first investigator-determined objective progression as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause in the absence of progressive disease. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment or date of randomization, whichever is later.

    Baseline to Objective Progression or Death Due to Any Cause (Up To 6.4 Months)

Secondary Outcomes (6)

  • Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)

    Baseline through Measured Progressive Disease (Up To 6.4 Months)

  • Duration of Response (DoR)

    Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 4.13 Months)

  • Complete Response (CR): Percentage of Participants Who Achieve CR

    Baseline Up to 6.94 months

  • Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)

    0.5 hours after the end of ramucirumab infusion on Day 1 of Cycle 1

  • PK: Minimum Serum Concentration of Ramucirumab (Cmin)

    Prior to ramucirumab infusion on Day 8 of Cycle 1, Day 1 of Cycle 2 and Day 1 of Cycle 5

  • +1 more secondary outcomes

Study Arms (2)

Ramucirumab + Gemcitabine + Docetaxel

EXPERIMENTAL

Participants received intravenous (IV) infusions of ramucirumab 9 milligrams per kilogram (mg/kg), gemcitabine 900 milligrams per meter square (mg/m2) on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.

Drug: RamucirumabDrug: GemcitabineDrug: Docetaxel

Gemcitabine + Docetaxel

ACTIVE COMPARATOR

Participants received intravenous infusions of gemcitabine 900 mg/m2 on days 1, 8, and docetaxel 75 mg/m2 on day 8 of a 21-day cycle until disease progression or a criterion for discontinuation were met.

Drug: GemcitabineDrug: Docetaxel

Interventions

Ramucirumab given IV

Also known as: LY3009806
Ramucirumab + Gemcitabine + Docetaxel

Gemcitabine given IV

Gemcitabine + DocetaxelRamucirumab + Gemcitabine + Docetaxel

Docetaxel given IV

Gemcitabine + DocetaxelRamucirumab + Gemcitabine + Docetaxel

Eligibility Criteria

Age12 Months - 29 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Participants must have discontinued all previous treatments for cancer or investigational agents ≥7 days after the last dose or per the type of previous treatment as stated in the protocol and must have recovered from the acute effects to ≤Grade 2 for alopecia and decreased tendon reflex and to ≤Grade 1 for all other effects at the time of enrollment, unless otherwise noted. Consult with the Lilly clinical research physician or scientist for the appropriate length of time prior to the first dose of study treatment.
  • Participants with relapsed, recurrent, or refractory SS.
  • Participants must:
  • Have measurable disease by Response Evaluation Criteria in Solid Tumors, Version (RECIST) 1.1.
  • have received at least one prior line of systemic treatment (including neoadjuvant and adjuvant chemotherapy) that contains ifosfamide and/or doxorubicin, or any approved therapies for which they are eligible, unless the patient is not a suitable candidate for the approved therapy.
  • not be eligible for surgical resection at time of enrollment.
  • Adequate cardiac function, defined as: Shortening fraction of ≥27% by echocardiogram, or ejection fraction of ≥50% by gated radionuclide study.
  • Adequate blood pressure (BP) control, defined as:
  • Participants ≥18 years: Controlled hypertension defined as systolic BP ≤150 millimeters of mercury (mmHg) or diastolic BP ≤90 mmHg where standard medical management is permitted. Please note that ≥2 serial BP readings should be obtained and averaged to determine baseline BP.
  • Participants \<18 years: A BP ≤95th percentile for age, height, and gender measured as described in National High Blood Pressure Education Program Working Group (NHBPEPWG) on High Blood Pressure in Children and Adolescents (2004), where standard medical management is permitted. Please note that ≥2 serial BP readings should be obtained and averaged to determine baseline BP.
  • Adequate hematologic function, as defined as:
  • Absolute neutrophil count (ANC): ≥750/microliters (µL) granulocyte-colony stimulating factor (G-CSF) permitted up to 48 hours prior. Participants with documented history of benign ethnic neutropenia or other conditions could be considered with a lower ANC after discussion with and approval from the Lilly clinical research physician or scientist.
  • Platelets: ≥75,000/cubic millimeters. Platelet transfusion permitted up to 72 hours prior.
  • Hemoglobin: ≥8 grams per deciliter (g/dL) (≥80 g/liter). Transfusions to increase the participant's hemoglobin level to at least 8 g/dL are permitted; however, study treatment must not begin until 7 days after the transfusion, and complete blood count criteria for eligibility are confirmed within 24 hr of first study dose.
  • Adequate renal function, as defined as:
  • +12 more criteria

You may not qualify if:

  • Participants with severe and/or uncontrolled concurrent medical disease or psychiatric illness/social situation that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol.
  • Participants who have active infections requiring therapy.
  • Participants with an active fungal, bacterial, and/or known severe viral infection including, but not limited to, human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
  • Participants who have had allogeneic bone marrow or solid organ transplant are excluded.
  • Surgery: Participants who have had, or are planning to have, the following invasive procedures are not eligible:
  • Major surgical procedure, laparoscopic procedure, or significant traumatic injury within 28 days prior to enrollment.
  • Central line placement or subcutaneous port placement is not considered major surgery.
  • Core biopsy, fine needle aspirate, and bone marrow biopsy/aspirate are not considered major surgeries.
  • Surgical or other wounds must be adequately healed prior to enrollment.
  • Bleeding and thrombosis:
  • Participants with evidence of active bleeding or a history of significant (≥Grade 3) bleeding event within 3 months prior to enrollment are not eligible.
  • Participants with a bleeding diathesis or vasculitis are not eligible.
  • Participants with known or prior history in the prior 3 months of esophageal varices are not eligible.
  • Participants with a history of deep vein thrombosis requiring medical intervention (including pulmonary embolism) within 3 months prior to study enrollment are not eligible.
  • Participants with a history of hemoptysis or other signs of pulmonary hemorrhage within 3 months prior to study enrollment are not eligible.
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (56)

Childrens Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202-5225, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Hospital

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Nationwide Children's Hosp

Columbus, Ohio, 43205-2664, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

Cook Children's Hospital

Fort Worth, Texas, 76104-2724, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital Research Foundation

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

The Sydney Children's Hospitals Network

Westmead, New South Wales, 2145, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UCL- Saint Luc

Brussels, 1200, Belgium

Location

Centre Leon Berard

Lyon, Auvergne-Rhône-Alpes, 69008, France

Location

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, 33076, France

Location

Institut Curie

Paris, 75248, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

Location

Azienda Ospedaliera Di Padova

Padua, 35128, Italy

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZT, Netherlands

Location

Prinses Maxima Centrum

Utrecht, 3584 CS, Netherlands

Location

Hospital Universitario Virgen Del Rocio

Seville, Andalusia, 41013, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Spain

Location

The Christie

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

University College Hospital - London

London, NW1 2PG, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M139WL, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Sarcoma, SynovialSarcoma

Interventions

RamucirumabGemcitabineDocetaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Limitations and Caveats

The limitation to this study was the highly varied estimates of the PFS HR and the probability of PFS HR \< 1 due to influence from the matched historical controls whose PFS substantially outperformed PFS from the prospectively randomized control.

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company

Study Officials

  • Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
GT60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 29, 2019

First Posted

October 31, 2019

Study Start

March 4, 2020

Primary Completion

February 23, 2023

Study Completion

February 23, 2023

Last Updated

September 13, 2023

Results First Posted

September 13, 2023

Record last verified: 2023-08

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
More information

Locations