Clinical Trials /

Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma

NCT04535713

Description:

This is an open label phase 2 study for advanced sarcoma using metronomic doses of gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given intravenously.

Related Conditions:
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab for Advanced Sarcoma
  • Official Title: A Phase 2 Study Using Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab as Second/Third Line Therapy for Advanced Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: SOC-2082
  • NCT ID: NCT04535713

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
GemcitabineGemzarSingle arm
DoxorubicinAdriamycinSingle arm
DocetaxelTaxotereSingle arm
NivolumabOpdivoSingle arm

Purpose

This is an open label phase 2 study for advanced sarcoma using metronomic doses of gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given intravenously.

Detailed Description

      This is an open label phase 2 study for advanced sarcoma using metronomic doses of
      gemcitabine, doxorubicin and docetaxel, and nivolumab immunotherapy given intravenously.

      A total of 260 patients will receive gemcitabine 600 mg/m2 (maximum dose: 1000 mg) on D1 and
      D8, doxorubicin 18 mg/m2 on D1 and D8 (maximum dose: 32 mg), docetaxel 25 mg/m2 on D1 and D8
      (maximum dose: 42 mg), on Days 1 and 8. After the first cycle, nivolumab 240 mg IV will be
      added on Day 1 of each cycle (see product information; www.accessdata.fda.gov). Treatment
      cycles are given every 3 weeks. Patients in this study may continue treatment until
      significant disease progression or unacceptable toxicity occurs up to one year of therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Single armExperimentalA total of 260 patients will receive gemcitabine 600 mg/m2 (maximum dose: 1000 mg) on D1 and D8, doxorubicin 18 mg/m2 on D1 and D8 (maximum dose: 32 mg), docetaxel 25 mg/m2 on D1 and D8 (maximum dose: 42 mg), on Days 1 and 8. After the first cycle, nivolumab 240 mg IV will be added on Day 1 of each cycle (see product information; www.accessdata.fda.gov). Treatment cycles are given every 3 weeks. Patients in this study may continue treatment until significant disease progression or unacceptable toxicity occurs up to one year of therapy. Patients who withdraw or do not complete the first 2 treatment cycles and first follow up CT scan/MRI will be replaced.
  • Gemcitabine
  • Doxorubicin
  • Docetaxel
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of locally advanced, unresectable or metastatic
             sarcoma

          -  Ability to understand the purposes and risks of the study and has signed and dated a
             written informed consent form approved by the Investigator's IRB/Ethics Committee

          -  Willingness to comply with all study procedures and availability for the duration of
             the study.

          -  Previously treated patient with measurable disease by RECIST v1.1

          -  ECOG performance status ≤ 2

          -  Life expectancy of at least 3 months

          -  Acceptable cardiac function with LV ejection fraction of > 50%

          -  Acceptable liver function: Bilirubin < 1.5 times upper limit of normal (ULN; except
             subjects with Gilbert Syndrome who must have a total bilirubin level < 3.0 ULN); AST
             (SGOT), ALT (SGPT) and alk phos < 2.5 x ULN (< 5 x ULN if liver metastases present)

          -  Acceptable renal function: Creatinine < 1.5 times ULN and creatinine clearance > 60
             ml/min using the Crockroft-Gault formula

          -  Acceptable hematologic status: ANC >1000 cells/μL; Platelet count >100,000/μL;
             Hemoglobin > 9.0 g/dL

          -  INR and PT < 1.5 ULN unless taking anti-coagulation, in which case PT, INR and aPTT
             must be within therapeutic range of intended use of anticoagulants

          -  All women of childbearing potential must have a negative urine or serum pregnancy test
             within 72 hours of enrollment. If urine test is positive or cannot be confirmed as
             negative, a serum pregnancy test will be required; all subjects must agree to use
             highly effective means of contraception (surgical sterilization or the use of barrier
             contraception with either a condom or diaphragm in conjunction with spermicidal gel or
             an IUD) with their partner from entry into the study through 5 months for women and 7
             months for men after the last dose.

        Exclusion Criteria:

          -  History or evidence of active autoimmune disease that requires systemic treatment (ie,
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement
             therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
             systemic treatment.

          -  Currently receiving treatment with another investigational device or drug study, or
             <14 days since ending treatment with another investigational device or drug study(s).

          -  Subject has known sensitivity to gemcitabine, doxorubicin, docetaxel or nivolumab.

          -  Female subject is pregnant or breast-feeding or planning to become pregnant during
             study treatment and through 3 months after the last dose of gemcitabine, doxorubicin,
             docetaxel or nivolumab.

          -  Female subject of childbearing potential who is unwilling to use acceptable method(s)
             of effective contraception during study treatment and through 3 months after the last
             dose of gemcitabine, doxorubicin, docetaxel or nivolumab.

          -  Sexually active subjects and their partners unwilling to use male or female latex
             condom
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:12 months
Safety Issue:
Description:Progression free survival from start of treatment to disease progression or death from any cause

Secondary Outcome Measures

Measure:Overall response
Time Frame:6 weeks
Safety Issue:
Description:Overall response by RECIST v1.1 via CT scan or MRI during the treatment period
Measure:Adverse Events
Time Frame:12 months
Safety Issue:
Description:Incidence of treatment related adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Oncology Research Center, LLC

Last Updated

November 12, 2020