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

Primary Purpose

Soft Tissue Sarcoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ipilimumab
Cryoablation
Nivolumab
Sponsored by
Kristen Ganjoo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Stanford Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ipilimumab/nivolumab + cryotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Clinical Response
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

Related Adverse Events (Toxicity)
Adverse events were assessed per CTCAE version 5. The outcome is those adverse events experienced by participants that were determined to be possibly, probably, or definitely-related to study treatment. Serious adverse events are identified by the term "SAE." Results are presented as the number of related adverse events by preferred term that occurred. The data are numbers without dispersion.
Immune-related Clinical Response (irRECIST) Rate
The immune-related (ir) clinical response will be assessed per the immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST) criteria, as follows: Complete response (CR) = Disappearance of all lesions, with any pathological lymph nodes having a reduction in short axis to < 10 mm; no new lesions > 5 × 5 mm in size. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) = Small changes that do not meet any of the these criteria; no new lesions > 5 × 5 mm in size. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions with the sum of diameters increasing ≥ 5 mm, and/or the appearance of 1+ new lesion(s). Note that irRECIST differs from RECIST criteria. The outcome is expressed as the total number of participants who achieve a ir-clinical response (ie, CR + PR) by 16 weeks, a number without dispersion.
Progression-free Survival (PFS)
Progression-free survival (PFS) is a measure of participants remaining alive without 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.

Full Information

First Posted
October 2, 2019
Last Updated
September 12, 2022
Sponsor
Kristen Ganjoo
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT04118166
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
April 6, 2021 (Actual)
Study Completion Date
March 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kristen Ganjoo
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this Phase 2 study is to find out if the study drugs (ipilimumab plus nivolumab) in combination with cryotherapy will help participants with metastatic or locally advanced soft tissue sarcoma;. find out how safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment. 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: Characterize the 6-month progression-free survival rate Assess whether the treatment yields a reasonably safe and tolerable profile

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ipilimumab/nivolumab + cryotherapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy, BMS-734016, MDX010, MDX-CTLA4
Intervention Description
Ipilimumab 1 mg/kg, injection
Intervention Type
Procedure
Intervention Name(s)
Cryoablation
Intervention Description
Cryoablation of the tumors occur between investigational agent treatment Cycles 1 and 2, and will be performed according to standard procedures
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, MDX1106, ONO-4538
Intervention Description
Nivolumab 3 mg/kg, injection
Primary Outcome Measure Information:
Title
Clinical Response
Description
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.
Time Frame
14 weeks
Secondary Outcome Measure Information:
Title
Related Adverse Events (Toxicity)
Description
Adverse events were assessed per CTCAE version 5. The outcome is those adverse events experienced by participants that were determined to be possibly, probably, or definitely-related to study treatment. Serious adverse events are identified by the term "SAE." Results are presented as the number of related adverse events by preferred term that occurred. The data are numbers without dispersion.
Time Frame
24 months
Title
Immune-related Clinical Response (irRECIST) Rate
Description
The immune-related (ir) clinical response will be assessed per the immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST) criteria, as follows: Complete response (CR) = Disappearance of all lesions, with any pathological lymph nodes having a reduction in short axis to < 10 mm; no new lesions > 5 × 5 mm in size. Partial response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions. Stable disease (SD) = Small changes that do not meet any of the these criteria; no new lesions > 5 × 5 mm in size. Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions with the sum of diameters increasing ≥ 5 mm, and/or the appearance of 1+ new lesion(s). Note that irRECIST differs from RECIST criteria. The outcome is expressed as the total number of participants who achieve a ir-clinical response (ie, CR + PR) by 16 weeks, a number without dispersion.
Time Frame
16 weeks
Title
Progression-free Survival (PFS)
Description
Progression-free survival (PFS) is a measure of participants remaining alive without 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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristen Ganjoo, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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