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
About this trial
This is an interventional treatment trial for Malignant Pleural Effusion
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
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
NCT ID
NCT05330065
First Posted
February 6, 2022
Last Updated
April 8, 2022
Sponsor
The First Affiliated Hospital of Zhengzhou University
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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