Clinical trial NCT05330065: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Malignant Pleural Effusion
Lead sponsor: The First Affiliated Hospital of Zhengzhou University
Sponsor class: OTHER
First posted: 2022-04-15
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events (Safety)
timeFrame: up to 12 months
measure: ORR
timeFrame: up to 12 months
Secondary outcomes:
measure: Exploratory biomarkers
timeFrame: up to 12 months
measure: Quality of life questionnaire EORTC QLQ 30
timeFrame: up to12 months
Other outcomes:
Locations:
Study officials:
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Feng Wang
role: PRINCIPAL_INVESTIGATOR
References: