Pegylated Liposomal Doxorubicin, PD-1 in Treating Muscle Invasive Bladder Cancer

A Non-randomized, Prospective Clinical Study of Pegylated Liposomal Doxorubicin and PD-1 in the Second-line Treatment of Relapse or Metastatic Muscle Invasive Bladder Cancer

Despite primary surgical management of muscle invasive bladder cancer (MIBC) with radical cystectomy and pelvic lymphnode dissection, up to 50% of patients will eventually develop tumours at distant sites, owing to pre-existing disseminated occult micrometastases. The first line treatment for relapse or metastatic MIBC is gemcitabine and cisplatin. After the failure of first line treatment, second line chemotherapy drugs can be chosen from doxorubicin, docetaxel, pemetrexed, etc. This non-randomized, prospective study aims to explore the efficacy and safety of PEGylated liposomal doxorubicin and PD-1 in second line treatment of MIBC.

Study Overview

• Status: Unknown
• Conditions: Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: pegylated liposomal doxorubicin (PLD); Drug: PD-1

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haitao Wang; Phone Number: (022)28331788; Email: peterrock2000@126.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical Unversity Second Hospital
      • Sub-Investigator: Lili Wang
      • Sub-Investigator: Dingkun Hou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinically confirmed muscle-invasive bladder cancer.
• Histologically confirmed by HE staining or IHC staining.
• Life expectancy of greater than or equal to 3 months.
• KPS performance >60, ECOG performance status ≤2.
• Adequate liver function with a bilirubin up to 1.5 x ULN. Transaminases up to 2.5 x ULN; for liver metastasis, transaminases up to 5 x ULN.
• Adequate bone marrow function, as defined by neutrophils count of ≥1.5×109/L, platelet count≥80×109/L, hemoglobin≥9.0g/dL.
• Adequate renal function (serum creatinine ≤1.25 times the ULN, and the release rate of which ≥ 60ml/min).
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Negative serum pregnancy test for female subjects with reproductive potential =< 7 days prior to registration, for women of childbearing potential only. All female patients of childbearing age and all male patients with partners of childbearing age should use a reliable method of contraception, such as the barrier method, throughout the study and for 8 weeks after last treatment.
• Sign the informed consent before any trial related activities.

Exclusion Criteria:

• A prior malignancy, other than non-melanoma skin cancer, carcinoma in situ, localized prostate cancer or ductal carcinoma in situ treated by surgery unless they have completed therapy at least 5 years prior to start of study and have no evidence of recurrent or residual disease
• Chemotherapy, biological therapy or other anti-cancer drugs ≤ 28 days prior to pre-registration
• Factors that would affect taking medicine orally, such as dysphagia, chronic diarrhea and intestinal obstruction
• History of arterial/venous thrombus ≤ 6 months prior to registration, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism
• History or tendency of gastrointestinal hemorrhage caused by severe gastroesophageal varices or other reasons.
• Dysfunction of blood coagulation: prothrombin time (PT)>16s, activated partial thromboplastin time (APTT) >43s, thrombin time (TT) >21s, INR >2, fibrinogen < 2g/L, bleeding tendency or under thrombolytic or anticoagulant therapy
• Uncontrolled intercurrent illness including, but not limited to:

ongoing or active infection; poor controlled diabetes (FBG > 10 mmol/L); urine protein ≥++, and UAE > 1.0g/24h; myocardial ischemia; congestive heart failure; cardiac arrhythmia or cardiac insufficiency; LVEF < 50%

• Unhealed wounds, ulcers or fractures
• Abuse of psychotropic substances or mentally disturbed
• History of HIV, organ transplantation or any other acquired, congenital immunodeficiency diseases
• Patients evaluated not suitable for the study in the opinion of investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group; Experimental group Pegylated liposomal doxorubicin 40mg/m2 iv every 3 weeks, for 3 cycles; PD-1 every 3 weeks, for 3 cycles.	Drug: pegylated liposomal doxorubicin (PLD); PLD is an anthracycline topoisomerase II inhibitor that is encapsulated in liposomes for intravenous use.; Other Names: Doxorubicin Hydrochloride Liposome Injection; Drug: PD-1; PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands and PD-L1.
ACTIVE_COMPARATOR: Control group; PD-1 every 3 weeks, for 6 cycles.	Drug: PD-1; PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands and PD-L1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	Disease control rate defined as confirmed complete response or partial response or stable disease under RECIST 1.0 criteria.	at least 10 months
Objective response rate	Objective response rate defined as confirmed complete response or partial response under RECIST 1.0 criteria.	at least 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression-free survival estimated using Kaplan-Meier methods is defined as the time from registration to the earlier of death or disease progression.	at least 10 months
Overall survival	Overall survival estimated using Kaplan-Meier methods is defined as the time from treatment initiation to death by any cause	at least 10 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Collaborators: CSPC Pharmaceutical Group Limited

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2019
• Primary Completion (ANTICIPATED): May 31, 2020
• Study Completion (ANTICIPATED): May 31, 2021

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 22, 2019
• First Posted (ACTUAL): September 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 26, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: DMSMIBC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No