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Cryoablation Combined With Tislelizumab Plus Lenvatinib in Patients With Melanoma Liver Metastasis

Primary Purpose

Melanoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Lenvatinib
Cryoablation
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma

Eligibility Criteria

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

Inclusion Criteria:

  1. Written informed consent obtained.
  2. Age ≥ 18 years at time of study entry.
  3. Participants must have melanoma liver metastasis.
  4. Participants must have failed 1 line of systemic regimens due to disease progression or toxicity.
  5. Participants who had received previous antiangiogenic therapy were eligible.
  6. At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI.
  7. Performance status (PS) ≤ 2 (ECOG scale).
  8. Life expectancy of at least 12 weeks.
  9. Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
  10. Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  11. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

Exclusion Criteria:

  1. History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
  2. Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
  3. Prior treatment with cryoablation.
  4. RFA and resection administered less then 4 weeks prior to study treatment start.
  5. Radiotherapy administered less then 4 weeks prior to study treatment start.
  6. Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
  7. Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
  8. Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  9. Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
  10. Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:

    1. history of interstitial lung disease
    2. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
    3. known acute or chronic pancreatitis
    4. active tuberculosis
    5. any other active infection (viral, fungal or bacterial) requiring systemic therapy
    6. history of allogeneic tissue/solid organ transplant
    7. diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of anti-PD1-monotherapy treatment.
    8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study.
    9. Live vaccine within 30 days prior to the first dose of anti-PD1 monotherapy treatment or during study treatment.
    10. History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of anti-PD1-monotherapy treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
  11. Medication that is known to interfere with any of the agents applied in the trial.
  12. Any other efficacious cancer treatment except protocol specified treatment at study start.
  13. Patient has received any other investigational product within 28 days of study entry.
  14. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  15. Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.

Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cryoablation in combination with Tislelizumab plus lenvatinib

Arm Description

Cryoablation treatment starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Outcomes

Primary Outcome Measures

ORR
Objective Response Rate according to RECIST 1.1

Secondary Outcome Measures

DCR
Disease control rate
DoR
Duration of response
TTR
Time to response
PFS
Progression Free Survival
OS
Overall survival
Adverse Events
Adverse event (AE)、Treatment emergent adverse event(TEAE)、Serious adverse event (SAE)

Full Information

First Posted
June 2, 2022
Last Updated
November 8, 2022
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05406466
Brief Title
Cryoablation Combined With Tislelizumab Plus Lenvatinib in Patients With Melanoma Liver Metastasis
Official Title
A Phase II Study of Cryoablation Combined With Tislelizumab Plus Lenvatinib in Patients With Melanoma Liver Metastasis (CASTLE-05)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2022 (Actual)
Primary Completion Date
July 10, 2024 (Anticipated)
Study Completion Date
August 16, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus lenvatinib in patients with melanoma liver metastasis.
Detailed Description
Recent studies have suggested that local destruction of tumor tissue by cryoablation induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed increased ORR in many type of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus lenvatinib in patients with melanoma liver metastasis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Cryoablation in combination with Tislelizumab plus lenvatinib
Arm Type
Experimental
Arm Description
Cryoablation treatment starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
a PD-1 immune check inhibitor
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Intervention Description
multitargeted receptor tyrosine kinase inhibitor
Intervention Type
Drug
Intervention Name(s)
Cryoablation
Intervention Description
Cryoablation will be performed with a two-cycle freeze-thaw phase protocol; US or non-contrast CT images will be obtained to visualize the evolving ablation zone
Primary Outcome Measure Information:
Title
ORR
Description
Objective Response Rate according to RECIST 1.1
Time Frame
max 24 months
Secondary Outcome Measure Information:
Title
DCR
Description
Disease control rate
Time Frame
max 24 months
Title
DoR
Description
Duration of response
Time Frame
max 24 months
Title
TTR
Description
Time to response
Time Frame
max 24 months
Title
PFS
Description
Progression Free Survival
Time Frame
max 24 months
Title
OS
Description
Overall survival
Time Frame
max 24 months
Title
Adverse Events
Description
Adverse event (AE)、Treatment emergent adverse event(TEAE)、Serious adverse event (SAE)
Time Frame
max 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent obtained. Age ≥ 18 years at time of study entry. Participants must have melanoma liver metastasis. Participants must have failed 1 line of systemic regimens due to disease progression or toxicity. Participants who had received previous antiangiogenic therapy were eligible. At least one measurable site of disease as defined by RECIST criteria with spiral CT scan or MRI. Performance status (PS) ≤ 2 (ECOG scale). Life expectancy of at least 12 weeks. Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula ) Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up. Exclusion Criteria: History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein. Prior treatment with cryoablation. RFA and resection administered less then 4 weeks prior to study treatment start. Radiotherapy administered less then 4 weeks prior to study treatment start. Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery. Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix. Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV). Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer. Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to: history of interstitial lung disease Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) known acute or chronic pancreatitis active tuberculosis any other active infection (viral, fungal or bacterial) requiring systemic therapy history of allogeneic tissue/solid organ transplant diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of anti-PD1-monotherapy treatment. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. Live vaccine within 30 days prior to the first dose of anti-PD1 monotherapy treatment or during study treatment. History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of anti-PD1-monotherapy treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS Medication that is known to interfere with any of the agents applied in the trial. Any other efficacious cancer treatment except protocol specified treatment at study start. Patient has received any other investigational product within 28 days of study entry. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
wangp413@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peng Wang, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
wangp413@163.com

12. IPD Sharing Statement

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Cryoablation Combined With Tislelizumab Plus Lenvatinib in Patients With Melanoma Liver Metastasis

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