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

NCT04118166 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-50853SARCOMA0038
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase 2 study is to

1. 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. 2.find out how safe are ipilimumab plus nivolumab given in combination with cryotherapy, and what side effects may be related to treatment.
3. 3.find out how do the study drugs in combination with cryotherapy work in soft tissue sarcoma.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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.

  14 weeks

Secondary Outcomes (3)

• Related Adverse Events (Toxicity)

  24 months

• Immune-related Clinical Response (irRECIST) Rate

  16 weeks

• Progression-free Survival (PFS)

  6 months

Study Arms (1)

Ipilimumab/nivolumab + cryotherapy

EXPERIMENTAL

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; Procedure: Cryoablation; Drug: Nivolumab

Interventions

Ipilimumab DRUG

Ipilimumab 1 mg/kg, injection

Also known as: Yervoy, BMS-734016, MDX010, MDX-CTLA4

Ipilimumab/nivolumab + cryotherapy

Cryoablation PROCEDURE

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

Ipilimumab/nivolumab + cryotherapy

Nivolumab DRUG

Nivolumab 3 mg/kg, injection

Also known as: BMS-936558, MDX1106, ONO-4538

Ipilimumab/nivolumab + cryotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unresectable or metastatic soft tissue sarcoma
• ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy
• Age ≥ 18 years
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Kristen Ganjoo: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Stanford Medical Center

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Ipilimumab; CTLA-4 Antigen; Cryosurgery; Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Maria Ahern
• Organization: Stanford Medicine at Stanford University

mahern@stanford.edu

650-725-6413

Study Officials

• Kristen Ganjoo, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 8, 2019
• Study Start: October 1, 2019
• Primary Completion: January 31, 2022
• Study Completion: April 26, 2022
• Last Updated: December 12, 2023
• Results First Posted: October 10, 2022

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)