- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04118166
Ipilimumab + Nivolumab + Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
Phase 2 Study of Ipilimumab Plus Nivolumab in Combination With Cryotherapy in Metastatic or Locally Advanced Soft Tissue Sarcoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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California
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Stanford, California, United States, 94304
- Stanford Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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
|
Ipilimumab 1 mg/kg, injection
Other Names:
Cryoablation of the tumors occur between investigational agent treatment Cycles 1 and 2, and will be performed according to standard procedures
Nivolumab 3 mg/kg, injection
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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:
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. |
14 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Related Adverse Events (Toxicity)
Time Frame: 24 months
|
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.
|
24 months
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Immune-related Clinical Response (irRECIST) Rate
Time Frame: 16 weeks
|
The immune-related (ir) clinical response will be assessed per the immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST) criteria, as follows:
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. |
16 weeks
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Progression-free Survival (PFS)
Time Frame: 6 months
|
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.
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kristen Ganjoo, MD, Stanford University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB-50853
- SARCOMA0038 (Other Identifier: OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Soft Tissue Sarcoma
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OHSU Knight Cancer InstituteNational Cancer Institute (NCI)WithdrawnStage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue Sarcoma | Stage IIA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma
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CytRxUnknownUnresectable Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Locally Advanced Soft Tissue SarcomaUnited States, Australia, Russian Federation, Hungary, India, Romania, Ukraine
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National Institutes of Health Clinical Center (CC)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma | Stage IVB Adult Soft Tissue Sarcoma
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National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue SarcomaUnited States
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UNICANCERRecruitingAdvanced Soft-tissue Sarcoma | Metastatic Soft-tissue SarcomaFrance
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University of Colorado, DenverAgenus Inc.RecruitingAdvanced Soft Tissue Sarcoma | Metastatic Soft Tissue SarcomaUnited States
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Wake Forest University Health SciencesMerck Sharp & Dohme LLCCompletedSoft Tissue Sarcoma, Adult | Soft Tissue Sarcoma, ChildUnited States
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