Clinical Trials /

Ipilimumab +Nivolumab + Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma

NCT04118166

Description:

The purpose of this Phase II study is to 1. find out if the study drugs (ipilimumab plus nivolumab) in combination with cryotherapy will help participants with metastatic or locally advanced soft tissue sarcoma;. 2. find out how safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment. 3. find out how do the study drugs in combination with cryotherapy work in soft tissue sarcoma.

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ipilimumab +Nivolumab + Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
  • Official Title: Phase 2 Study of Ipilimumab Plus Nivolumab in Combination With Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: IRB-50853
  • SECONDARY ID: SARCOMA0038
  • SECONDARY ID: IRB-50853
  • NCT ID: NCT04118166

Conditions

  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
IpilimumabYervoy, BMS-734016, MDX010, MDX-CTLA4Ipilimumab/nivolumab+ cryotherapy
NivolumabBMS-936558, MDX1106, ONO-4538Ipilimumab/nivolumab+ cryotherapy

Purpose

The purpose of this Phase II study is to 1. find out if the study drugs (ipilimumab plus nivolumab) in combination with cryotherapy will help participants with metastatic or locally advanced soft tissue sarcoma;. 2. find out how safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment. 3. find out how do the study drugs in combination with cryotherapy work in soft tissue sarcoma.

Detailed Description

      Primary Objectives:

      1) Assess whether the rate of clinical benefit is sufficiently high to merit promise for
      further study

      Secondary Objectives:

        1. Characterize the 6-month progression-free survival rate

        2. Assess whether the treatment yields a reasonably safe and tolerable profile
    

Trial Arms

NameTypeDescriptionInterventions
Ipilimumab/nivolumab+ cryotherapyExperimental1 mg/kg with nivolumab 3 mg/kg every 3 weeks x 4 doses. (One cycle of treatment is 3 weeks). Cryotherapy (cryoablation) will be performed between investigational agent treatment Cycles 1 and 2
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Unresectable or metastatic soft tissue sarcoma

          -  ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy

          -  Age ≥ 18 years

          -  4 Life expectancy > 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Lab values as below:

        Absolute neutrophil count (ANC) ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3; Creatinine ≤ 1.5
        x upper limit of normal (ULN) OR calculated (calc.); creatinine clearance > 45 mL/min using
        the lean body mass formula only; Total bilirubin ≤ 1.5 x ULN in absence of Gilbert disease
        (total bilirubin ≤ 3 x ULN with Gilbert); also, if hyperbilirubinemia is clearly attributed
        to liver metastases total bilirubin ≤ 3 x ULN is permitted AST/ALT ≤ 3 x ULN;Thyroid
        stimulating hormone (TSH) within normal limits (WNL);supplementation is acceptable to
        achieve a TSH WNL; in subjects with abnormal TSH if free T4 is normal and subject is
        clinically euthyroid, subject is eligible

          -  Any toxic effects of prior therapy (except alopecia) must be resolved to NCI CTCAE,
             version 5.0, Grade 1 or less

          -  Ability to understand and the willingness to sign a written informed consent

          -  Women of childbearing potential (WOCBP) receiving nivolumab must be willing to adhere
             to contraception for a period of 5 months after the last dose of nivolumab. Men
             receiving nivolumab and who are sexually active with WOCBP will be instructed and must
             be willing to adhere to contraception for a period of 7 months after the last dose of
             nivolumab.

        Exclusion Criteria:

          -  Prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell
             death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

        History of the following:

          -  Active known or suspected autoimmune disease

          -  Known human immunodeficiency virus (HIV) (Subjects with lymphocytes > 350 cluster of
             differentiation (CD)4+ cells and no detectable viral load are eligible)

          -  Hepatitis B

        Hepatitis B can be defined as:

        Hepatitis B surface antigen (HBsAg) > 6 months Serum hepatitis B virus (HBV)
        deoxyribonucleic acid (DNA) 20,000 IU/mL (105 copies/mL), lower values 2,000 to 20,000
        IU/mL (104 to 105 copies/mL) are often seen in hepatitis B-e antigen (HbeAg)-negative
        chronic hepatitis B Persistent or intermittent elevation in alanine aminotransferase
        (ALT)/alanine aminotransferase (AST) levels. Liver biopsy showing chronic hepatitis with
        moderate or severe necroinflammation

          -  Hepatitis C Hepatitis C antibody (Ab) positive Presence of hepatitis C virus (HCV)
             ribonucleic acid (RNA) 3.2.2.5 Known active pulmonary disease with hypoxia defined as:
             Oxygen saturation < 85% on room air or Oxygen saturation < 88% despite supplemental
             oxygen

          -  Systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents)
             or other immunosuppressive medications within 7 days of registration

          -  Received any live/attenuated vaccine (eg, varicella, zoster, yellow fever, rotavirus,
             oral polio and measles, mumps, rubella (MMRI) within 30 days before initiation of
             treatment on this protocol.

          -  If female, pregnant or lactating. (Women of childbearing potential are required to
             have a negative pregnancy test within 24 hours prior to the initial administration of
             study drug)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Response Rate
Time Frame:16 weeks
Safety Issue:
Description:Clinical response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria: Complete response (CR) = Disappearance of all target lesions; all lymph nodes < 10 mm on the short axis; no new lesions. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; no new lesions. Stable disease (SD) = Small changes that do not meet any of the above criteria; no new lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s). Clinical Response Rate =CR+PR. The outcome is expressed as the total number of participants who achieve a clinical response by 16 weeks, a number without dispersion.

Secondary Outcome Measures

Measure:Partial Response (PR) Rate
Time Frame:16 weeks
Safety Issue:
Description:Clinical response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete response (CR) = Disappearance of all target lesions; no new lesions. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; no new lesions. Stable disease (SD) = Small changes that do not meet any of the above criteria; no new lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) The outcome is expressed as the total number of participants who achieve PR by 16 weeks, a number without dispersion.
Measure:Stable Disease (SD) Rate
Time Frame:16 weeks
Safety Issue:
Description:Clinical response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete response (CR) = Disappearance of all target lesions; no new lesions. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; no new lesions. Stable disease (SD) = Small changes that do not meet any of the above criteria; no new lesions. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) The outcome is expressed as the total number of participants with SD at 16 weeks, a number without dispersion.
Measure:Related Adverse Events (Toxicity)
Time Frame:24 months
Safety Issue:
Description:Adverse events were assessed per CTCAE version 5. The outcome is expressed as the total number of possibly, probably, or definitely-related adverse events experienced by participants, a number without dispersion.
Measure:Immune-related Clinical Response (irRECIST) rate
Time Frame:16 weeks
Safety Issue:
Description:The Immune-related Response will be assessed per the irRECIST criteria: Complete response (CR) = Disappearance of all target lesions; no new lesions > 5 × 5 mm in size. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; no new lesions > 5 × 5 mm in size. Stable disease (SD) = Small changes that do not meet any of the above criteria; no new lesions > 5 × 5 mm in size. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s). irRECIST clinical response rate =CR+PR. The outcome is expressed as the total number of participants who achieve a clinical response by 16 weeks, a number without dispersion.
Measure:Progression-free survival
Time Frame:6 months
Safety Issue:
Description:Progression-free survival (PFS) as measured from the time of consent until death or disease progression. The outcome is expressed as the total number of participants remaining alive without disease progression at 6 months after consent, a number without dispersion.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Stanford University

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