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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04118166
Recruitment Status : Active, not recruiting
First Posted : October 8, 2019
Last Update Posted : February 18, 2022
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Kristen Ganjoo, Stanford University

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Drug: Ipilimumab Procedure: Cryoablation Drug: Nivolumab Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of Ipilimumab Plus Nivolumab in Combination With Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
Actual Study Start Date : October 1, 2019
Actual Primary Completion Date : April 6, 2021
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ipilimumab/nivolumab+ cryotherapy
1 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
Drug: Ipilimumab
Ipilimumab 1 mg/kg, injection
Other Names:
  • Yervoy
  • BMS-734016
  • MDX010
  • MDX-CTLA4

Procedure: Cryoablation
Cryoablation of the tumors occur between investigational agent treatment Cycles 1 and 2, and will be performed according to standard procedures

Drug: Nivolumab
Nivolumab 3 mg/kg, injection
Other Names:
  • BMS-936558
  • MDX1106
  • ONO-4538




Primary Outcome Measures :
  1. Clinical Response [ Time Frame: 14 weeks ]

    Clinical benefit was assessed on the basis of clinical response 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 benefit was defined as CR + PR. The primary outcome is expressed as the total number of participants who receive clinical benefit within 14 weeks, a number without dispersion. Rates of all clinical responses are reported.



Secondary Outcome Measures :
  1. Related Adverse Events (Toxicity) [ Time Frame: 24 months ]
    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.

  2. Immune-related Clinical Response (irRECIST) rate [ Time Frame: 16 weeks ]

    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.


  3. Progression-free survival [ Time Frame: 6 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

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): NCT04118166


Locations
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United States, California
Stanford Medical Center
Stanford, California, United States, 94304
Sponsors and Collaborators
Kristen Ganjoo
Bristol-Myers Squibb
Investigators
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Principal Investigator: Kristen Ganjoo, MD Stanford University
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Responsible Party: Kristen Ganjoo, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT04118166    
Other Study ID Numbers: IRB-50853
SARCOMA0038 ( Other Identifier: OnCore )
IRB-50853 ( Other Identifier: Stanford IRB )
First Posted: October 8, 2019    Key Record Dates
Last Update Posted: February 18, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action