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A Study of Intrapleural Administration of Bevacizumab and Camrelizumab for Malignant Pleural Effusion

Primary Purpose

Malignant Pleural Effusion

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
bevacizumab and camrelizumab
Sponsored by
The First Affiliated Hospital of Zhengzhou University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Effusion

Eligibility Criteria

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

Inclusion Criteria:

  1. Be ≥ 18 years of age on day of signing informed consent.
  2. Histologically or cytologically documented malignant pleural effusion
  3. Histologically confirmed cancer
  4. Malignant pleural effusion clinically judged as not responsive to conventional systemic therapy(ies) for primary malignancy
  5. Adequate liver and renal function as defined below:
  6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  7. Life expectancy of > 12 weeks
  8. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
  9. Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study.
  10. Willing and able to comply with all study procedures

Exclusion Criteria:

  1. Receiving any investigational agent, or using an investigational device, currently or within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is longer.
  2. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.
  3. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1, or who has not recovered to, ≤ Grade 1 toxicity at baselines from adverse events due to agents administered more than 4 weeks earlier.
  4. Has received prior intrapleural administration with an anti-programmed cell death receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  5. Has received prior intrapleural administration with bevacizumab or Endostar.
  6. Any concurrent chemotherapy, intraperitoneal (IP), biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  7. Major surgery within 28 days prior to day 1 of study treatment from which the patient has not completely recovered.
  8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  9. Has a history of non-infectious pneumonitis that required steroids; currently active non-infectious pneumonitis; or evidence of interstitial lung disease.
  10. Has an active infection requiring systemic therapy or history of uncontrolled infection.
  11. Concurrent disease or condition which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results
  12. Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Bevacizumab and Camrelizumab for Malignant Pleural Effusion

    Arm Description

    Outcomes

    Primary Outcome Measures

    Adverse Events (Safety)
    Incidence of safety events including: adverse events (AEs), Serious AEs, and dose limiting toxicities (DLTs) AEs:Percentage of participants with adverse events; SAEs:Percentage of participants with Serious AEs; Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.0 criteria.
    ORR
    Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when >50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR

    Secondary Outcome Measures

    Exploratory biomarkers
    The expression levels of PD-L1 CPS and TPS in baseline Tumor cells embedded in initial pleural fluid sediment Levels of VEGF and its soluble receptor SVEGFR-1 in pleural fluid and plasma (THE levels of VEGF and SVEGFR-1 in pleural fluid and plasma are determined by ELISA) ; Flow cytometry is used to detect CD8+ CD69+ cell , CD8+ IFN-G + cell , CD8+ Granzyb + cell and CD8+ PD-1+ in MPE before and after intrathoracic injection of the study drug.; The release levels of TNF-A and IL-1B in the supernatant of pleural effusion and peripheral blood using ELISA
    Quality of life questionnaire EORTC QLQ 30
    Scale from 1-100 for 30 items, higher score indicates a better situation.

    Full Information

    First Posted
    February 6, 2022
    Last Updated
    April 8, 2022
    Sponsor
    The First Affiliated Hospital of Zhengzhou University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05330065
    Brief Title
    A Study of Intrapleural Administration of Bevacizumab and Camrelizumab for Malignant Pleural Effusion
    Official Title
    A Phase Ib/II Study of Intrapleural Administration of Bevacizumab and Camrelizumab for Patients With Malignant Pleural Effusion
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    August 1, 2022 (Anticipated)
    Primary Completion Date
    August 31, 2023 (Anticipated)
    Study Completion Date
    August 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The First Affiliated Hospital of Zhengzhou 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
    Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. The combined use of anti-angiogenic therapy and immunotherapy may be a promising strategy for MPE. This is a Phase Ib/II clinical trial to evaluate the safety and tolerability of administering bevacizumab and camrelizumab into the intrapleural space of subjects with malignant pleural effusion through a pleurX catheter.
    Detailed Description
    This study is a phase Ib/II, single arm study with main purpose to evaluate the safety, tolerability and efficacy of intrapleural administration of bevacizumab and camrelizumab in subjects with malignant pleural effusion. The study aims to recruit 9 - 15 subjects in phase 1, and once the safety, tolerability and the preliminary efficacy of bevacizumab and camrelizumab reach an optimal target exposure for recommended dose (RD), phase 2a will be opened for enrolment of approximately 40 subjects

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Malignant Pleural Effusion

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    55 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Bevacizumab and Camrelizumab for Malignant Pleural Effusion
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    bevacizumab and camrelizumab
    Intervention Description
    Stage 1 was classical "3+3" dose escalation with pts assigned to one of the following 3 cohorts, Cohort A:Avastin 5mg/kg once every 2 weeks and camrelizumab 100mg once every 2 weeks;Cohort B:Avastin 7.5mg/kg once every 2 weeks and camrelizumab 100mg once every 2 weeks;Cohort C:Avastin 7.5mg/kg once every 2 weeks and camrelizumab 200mg once every 2 weeks.DLT was observed for 28 days.
    Primary Outcome Measure Information:
    Title
    Adverse Events (Safety)
    Description
    Incidence of safety events including: adverse events (AEs), Serious AEs, and dose limiting toxicities (DLTs) AEs:Percentage of participants with adverse events; SAEs:Percentage of participants with Serious AEs; Dose limiting toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.0 criteria.
    Time Frame
    up to 12 months
    Title
    ORR
    Description
    Complete remission (CR) was considered when the accumulated fluid had disappeared and was stable for at least four weeks; partial remission (PR) was considered when >50% of the accumulated fluid had disappeared, symptoms had improved, and the remaining fluid had failed to increase for at least four weeks; The total efficiency ORR was calculated by taking the sum of CR+PR
    Time Frame
    up to 12 months
    Secondary Outcome Measure Information:
    Title
    Exploratory biomarkers
    Description
    The expression levels of PD-L1 CPS and TPS in baseline Tumor cells embedded in initial pleural fluid sediment Levels of VEGF and its soluble receptor SVEGFR-1 in pleural fluid and plasma (THE levels of VEGF and SVEGFR-1 in pleural fluid and plasma are determined by ELISA) ; Flow cytometry is used to detect CD8+ CD69+ cell , CD8+ IFN-G + cell , CD8+ Granzyb + cell and CD8+ PD-1+ in MPE before and after intrathoracic injection of the study drug.; The release levels of TNF-A and IL-1B in the supernatant of pleural effusion and peripheral blood using ELISA
    Time Frame
    up to 12 months
    Title
    Quality of life questionnaire EORTC QLQ 30
    Description
    Scale from 1-100 for 30 items, higher score indicates a better situation.
    Time Frame
    up to12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Be ≥ 18 years of age on day of signing informed consent. Histologically or cytologically documented malignant pleural effusion Histologically confirmed cancer Malignant pleural effusion clinically judged as not responsive to conventional systemic therapy(ies) for primary malignancy Adequate liver and renal function as defined below: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Life expectancy of > 12 weeks Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study. Willing and able to comply with all study procedures Exclusion Criteria: Receiving any investigational agent, or using an investigational device, currently or within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is longer. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1, or who has not recovered to, ≤ Grade 1 toxicity at baselines from adverse events due to agents administered more than 4 weeks earlier. Has received prior intrapleural administration with an anti-programmed cell death receptor (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Has received prior intrapleural administration with bevacizumab or Endostar. Any concurrent chemotherapy, intraperitoneal (IP), biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. Major surgery within 28 days prior to day 1 of study treatment from which the patient has not completely recovered. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Has a history of non-infectious pneumonitis that required steroids; currently active non-infectious pneumonitis; or evidence of interstitial lung disease. Has an active infection requiring systemic therapy or history of uncontrolled infection. Concurrent disease or condition which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Wang Wang
    Phone
    13938244776
    Email
    zzuwangfeng@zzu.edu.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Feng Wang
    Organizational Affiliation
    The First Affiliated Hospital of Zhengzhou University
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    A Study of Intrapleural Administration of Bevacizumab and Camrelizumab for Malignant Pleural Effusion

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