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

Phase 1

Not yet recruiting

• Conditions: Malignant Pleural Effusion
• Interventions: Drug: bevacizumab and camrelizumab

• Registration Number: NCT05330065
• Lead Sponsor: The First Affiliated Hospital of Zhengzhou University

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

Study Timeline

• Study First Submitted: 2022-02-06
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-08
• Last Update Submitted: 2022-04-08
• Study First Posted: 2022-04-15
• Last Update Posted: 2022-04-15
• Study Start: 2022-08-01
• Primary Completion: 2023-08-31
• Study Completion: 2024-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bevacizumab and Camrelizumab for Malignant Pleural Effusion	bevacizumab and camrelizumab	-

Primary Outcome Measures

Name	Time	Method
ORR	up to 12 months	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
Adverse Events (Safety)	up to 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Quality of life questionnaire EORTC QLQ 30	up to12 months	Scale from 1-100 for 30 items, higher score indicates a better situation.
Exploratory biomarkers	up to 12 months	1. The expression levels of PD-L1 CPS and TPS in baseline Tumor cells embedded in initial pleural fluid sediment; 2. 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) ; 3. 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.; 4. The release levels of TNF-A and IL-1B in the supernatant of pleural effusion and peripheral blood using ELISA