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Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine

Primary Purpose

Bladder Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Catumaxomab
Sponsored by
LintonPharm Co.,Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Bladder Cancer, Failed or are Intolerant to BCG Vaccine, catumaxomab

Eligibility Criteria

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

Inclusion Criteria:

  1. Signed and dated informed consent forms have been provided.
  2. Willing to be complaint with the study procedures during the study.
  3. Male or female, age ≥ 18 years old when signing informed consents.
  4. Histologically or cytologically diagnosed as NMIBC, i.e., bladder cancer in the following pTNM status: pTis, pTa, pT1.
  5. Have received the standard therapy recommended in the current NMIBC clinical guidelines, including intravesical BCG instillation, and diagnosed as BCG failure or intolerance.
  6. Have undergone standard TURBT + immediate intravesical chemotherapy before the signing of ICF, with the absence of visible tumor lesion residues in the surgical field.
  7. Recovered from any toxicity due to previous treatment (Grade 0-1 according to NCI-CTCAE v 5.0).
  8. Estimated life span is ≥ 6 months.
  9. Eastern Oncology Cooperative Group (ECOG) performance status 0-1.
  10. The laboratory test values during the screening period are in accordance with the following table:

    • ANC(absolute neutrophil count)>=1.5x10^9/L
    • Hemoglobin>=80 g/L
    • Platelet>=100x10^9/L
    • Lymphocyte percentage>=20%
    • Serum Bilirubin <=1.25
    • ULN(or 2.5 ULN if there is Gilbert)
    • AST and ALT <=2.5 ULN without liver metastasis(or<=5 ULN if liver metastasis)
    • Serum creatinine <=2.0 mg/dL or
    • Calculated creatinine clearance>=30 mL/min.
  11. For women of childbearing potential: use an efficient method for contraception at least 1 month prior to screening and agree to use this method for contraception during the study period and 30 days after the last intravesical instillation.;
  12. For men with fertility potential: use condoms or other methods to ensure effective contraception for sexual partners from screening to 30 days after the last intravesical instillation.

Exclusion Criteria:

  1. Known or suspected of being allergic to catumaxomab or similar antibodies.
  2. Besides the TURBT + immediate postoperative infusion chemotherapy for this NMIBC recurrence, participants received other anti-tumor treatments, including other anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents, hormone therapy, radiation therapy (excluding local radiation therapy for pain relief), etc., the interval between the last instillation and the first intravesical instillation is ≤ 21 days.
  3. Tumor metastases outside the bladder confirmed in imaging examination.
  4. With other primary malignant tumors diagnosed before the signing of ICF, excluding squamous cell carcinoma in situ of skin or cervical carcinoma in situ without recurrence within 5 years after resection.
  5. The following diseases have not been resolved to CTCAE grade 0-1 in 3 days prior to the first instillation:

    • Uncontrolled acute and chronic infections such as pneumonia, biliary infection, hepatitis B virus infection and hepatitis C virus infection, etc.
    • Dyspnea.
    • Acute /chronic renal injury.
    • Nephrotic syndrome.
    • Bladder perforation.
    • Urinary tract obstruction.
  6. NYHA Class 3 or 4.
  7. Related symptoms and signs of cardiovascular diseases: including myocardial infarction, congestive heart failure, and arrhythmia.
  8. Known cerebrovascular accidents.
  9. History of autoimmune diseases (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autologous hemolytic anemia, rheumatoid arthritis, etc.).
  10. Patients with known HIV serology positive, hepatitis C infection and/or hepatitis B (Except the patients with positive HepBsAg or core antibody are responding to anti-HBV treatment, they are allowed to participate in the study.

    Notes: HepBsAg-negative patients at screening, or patients are undergoing treatment with interferon-2a [IFN] or peginterferon-2a [Peg-IFN] and hepatitis B virus [HBV] DNA < 2000 international units [IU], or partients who are receiving nucleoside [acid] analogues at screening and HBV DNA below the lower limit of normal [LLN] are eligible to participate in the study.

  11. Pregnancy or breastfeeding during study treatment and follow-up period.
  12. Patients with confirmed past history of neurological or psychotic disorders, including epilepsy or dementia.
  13. Other serious systemic conditions that may limit the participation in this study (e.g. uncontrolled diabetes, cardiovascular and cerebrovascular disease, severe gastrointestinal disease, and renal disease, etc.).

Sites / Locations

  • The First Affiliated Hospital,Sun Yat-sen UniversityRecruiting
  • Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityRecruiting
  • Peking University Third HospitalRecruiting
  • Sun Yat-sen University Cancer CenterRecruiting
  • The Second Hospital of Tianjin Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Catumaxomab

Arm Description

In the dose escalation phase, 2 dose levels of catumaxomab will be explored.

Outcomes

Primary Outcome Measures

Dose escalation phase and dose expansion phase only: DLT incidence.
Dose Limited Toxicity
1-year recurrence rate since the initial instillation
1-year recurrence rate since the initial instillation

Secondary Outcome Measures

Recurrence rate at 3 months / 6 months / 2 years.
Recurrence rate at 3 months / 6 months / 2 year
PFS
Relapse-free survival
2-year progression rate to MIBC.
2-year progression rate to MIBC.
The incidence and severity of treatment-emergent adverse events (TEAEs) and Serious adverse event(SAE)
The incidence and severity of treatment-emergent adverse events (TEAEs) and Serious adverse event(SAE) during intravesical instillation with catumaxomab are observed according to the National Cancer Institute Common Terminology Standard for Adverse Events (NCI-CTCAE) v5.0.
ADA
the incidence of anti-drug antibodies (ADA) to catumaxomab by intravesical instillation in serum.
Pharmacokinetic parameters-Cmax
Pharmacokinetic parameters Cmax of bladder perfusion of Catumaxomab in plasma and urine
Pharmacokinetic parameters-Cmin
Pharmacokinetic parameters Cmin of bladder perfusion of Catumaxomab in plasma and urine
Pharmacokinetic parameters-AUC
Pharmacokinetic parameters-AUC of bladder perfusion of Catumaxomab in plasma and urine
Pharmacokinetic parameters-t1/2
Pharmacokinetic parameters-t1/2 of bladder perfusion of Catumaxomab in plasma and urine

Full Information

First Posted
March 12, 2021
Last Updated
February 9, 2023
Sponsor
LintonPharm Co.,Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT04799847
Brief Title
Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine
Official Title
A Multicenter, Non-randomized, Uncontrolled, Open-label Phase I/II Study to Observe the Safety and Preliminary Efficacy of Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 23, 2021 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LintonPharm Co.,Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A Multicenter, Non-randomized, Uncontrolled, Open-label Phase I/II study to Observe the Safety and Preliminary Efficacy of Catumaxomab in Patients with Non-Muscle-Invasive Bladder Cancer who have Failed or are Intolerant to Bacillus Calmette-Guerin (BCG) Vaccine
Detailed Description
This is a multicenter, non-randomized, uncontrolled, open-label phase I/II study to observe the safety and preliminary efficiency of catumaxomab in patients (hereinafter referred to as participants) with non-muscle-invasive bladder cancer (NMIBC) who have failed or are intolerant to Bacillus Calmette-Guerin (BCG) vaccine. This study is conducted in 3 phases sequentially: dose escalation phase, dose expansion phase and dose extension phase. In the dose escalation phase, the preliminary safety and pharmacokinetic profile of catumaxomab for 4 cycles of instillation in 20ug group participants and 2cycles of instillation in 100ug group participants are explored. Data will be collected after completing DLT observation in all cohorts, but it is not required to lock database. DSMB will review the data of each dose cohort and decide whether to open the enrollment for the next cohort. DSMB will recommend the dose at dose expansion phase according to the relevant data after the completion of DLT observation and the first efficiency assessment. In the dose expansion phase, 24 participants will receive the catumaxomab treatment at dosing scheme recommended by the DSMB. DLT events occurred within 28 days after the initial instillation will be investigated. After th DLT observation period, DSMB will evaluate the data from both dose escalation and dose expansion phase and decide whether to initiate the dose extension phase; protocol amendment might be developed. In the dose extension phase, the elgible participants are enrolled and allocated into three arms according to the type of BCG treatment failure: refractory, relapse, and intolerance. A maximum 125 participants are enrolled in the 3 arms, with at least 30 participants allocated to each. The participants will have chest and abdominal CT and pelvic MRI scan at baseline to determine the area of lesion and to rule out possible extra-bladder lesions. From the initial instillation, cystoscopy, bladder biopsy, urinary cytology, and pelvic MRI scan are performed every 12 weeks (±7 days); chest and abdominal CT scans are performed every 24 weeks (±7 days)1 until recurrence, progression, consent withdrawal, or 96 weeks (±7 days) from the initial instillation, whichever occurs firstly. Participants who discontinue study treatment early due to any reasons other than disease progression will continue to have the tumor response assessment as planned until the participant has disease progression, withdrawal of consent, loss of follow-up, death, 96 weeks (± 7 days) after the initial instillation or until the end of the study, whichever occurs firstly.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
Bladder Cancer, Failed or are Intolerant to BCG Vaccine, catumaxomab

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Catumaxomab
Arm Type
Experimental
Arm Description
In the dose escalation phase, 2 dose levels of catumaxomab will be explored.
Intervention Type
Drug
Intervention Name(s)
Catumaxomab
Intervention Description
This study is conducted in 3 phases sequentially: dose escalation phase, dose expansion phase and dose extension phase. In the dose escalation phase, the preliminary safety and pharmacokinetic profile of catumaxomab by instillation, at 2 dose levels(20ug group and 100ug group), in NMIBC patients are investigated.
Primary Outcome Measure Information:
Title
Dose escalation phase and dose expansion phase only: DLT incidence.
Description
Dose Limited Toxicity
Time Frame
28 days
Title
1-year recurrence rate since the initial instillation
Description
1-year recurrence rate since the initial instillation
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Recurrence rate at 3 months / 6 months / 2 years.
Description
Recurrence rate at 3 months / 6 months / 2 year
Time Frame
Up to 2 years
Title
PFS
Description
Relapse-free survival
Time Frame
2 years
Title
2-year progression rate to MIBC.
Description
2-year progression rate to MIBC.
Time Frame
2 years
Title
The incidence and severity of treatment-emergent adverse events (TEAEs) and Serious adverse event(SAE)
Description
The incidence and severity of treatment-emergent adverse events (TEAEs) and Serious adverse event(SAE) during intravesical instillation with catumaxomab are observed according to the National Cancer Institute Common Terminology Standard for Adverse Events (NCI-CTCAE) v5.0.
Time Frame
2 years
Title
ADA
Description
the incidence of anti-drug antibodies (ADA) to catumaxomab by intravesical instillation in serum.
Time Frame
2 years
Title
Pharmacokinetic parameters-Cmax
Description
Pharmacokinetic parameters Cmax of bladder perfusion of Catumaxomab in plasma and urine
Time Frame
2 years
Title
Pharmacokinetic parameters-Cmin
Description
Pharmacokinetic parameters Cmin of bladder perfusion of Catumaxomab in plasma and urine
Time Frame
2 years
Title
Pharmacokinetic parameters-AUC
Description
Pharmacokinetic parameters-AUC of bladder perfusion of Catumaxomab in plasma and urine
Time Frame
2 years
Title
Pharmacokinetic parameters-t1/2
Description
Pharmacokinetic parameters-t1/2 of bladder perfusion of Catumaxomab in plasma and urine
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed and dated informed consent forms have been provided. Willing to be complaint with the study procedures during the study. Male or female, age ≥ 18 years old when signing informed consents. Histologically or cytologically diagnosed as NMIBC, i.e., bladder cancer in the following pTNM status: pTis, pTa, pT1. Have received the standard therapy recommended in the current NMIBC clinical guidelines, including intravesical BCG instillation, and diagnosed as BCG failure or intolerance. Participants had completed TURBT or cystoscopy as required by guidelines prior to enrollment, and no significant tumours were seen in the surgical field Residual lesions Recovered from any toxicity due to previous treatment (Grade 0-1 according to NCI-CTCAE v 5.0). Estimated life span is ≥ 6 months. Eastern Oncology Cooperative Group (ECOG) performance status 0-1. The laboratory test values during the screening period are in accordance with the following table: ANC(absolute neutrophil count)>=1.5x10^9/L Hemoglobin>=80 g/L Platelet>=100x10^9/L Lymphocyte percentage>=20% Serum Bilirubin <=1.25 ULN(or 2.5 ULN if there is Gilbert) AST and ALT <=2.5 ULN without liver metastasis(or<=5 ULN if liver metastasis) Serum creatinine <=2.0 mg/dL or Calculated creatinine clearance>=30 mL/min. For women of childbearing potential: use an efficient method for contraception at least 1 month prior to screening and agree to use this method for contraception during the study period and 30 days after the last intravesical instillation.; For men with fertility potential: use condoms or other methods to ensure effective contraception for sexual partners from screening to 30 days after the last intravesical instillation. Exclusion Criteria: Known or suspected of being allergic to catumaxomab or similar antibodies. Besides the TURBT + immediate postoperative infusion chemotherapy for this NMIBC recurrence, participants received other anti-tumor treatments, including other anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents, hormone therapy, radiation therapy (excluding local radiation therapy for pain relief), etc., the interval between the last instillation and the first intravesical instillation is ≤ 21 days. Tumor metastases outside the bladder confirmed in imaging examination. With other primary malignant tumors diagnosed before the signing of ICF, excluding squamous cell carcinoma in situ of skin or cervical carcinoma in situ without recurrence within 5 years after resection. The following diseases have not been resolved to CTCAE grade 0-1 in 3 days prior to the first instillation: Uncontrolled acute and chronic infections such as pneumonia, biliary infection, hepatitis B virus infection and hepatitis C virus infection, etc. Dyspnea. Acute /chronic renal injury. Nephrotic syndrome. Bladder perforation. Urinary tract obstruction(except benign prostatic hypertrophy). NYHA Class 3 or 4. Related symptoms and signs of cardiovascular diseases have not been resolved to CTCAE grade 0-1: including myocardial infarction, congestive heart failure, and arrhythmia. Known cerebrovascular accidents have not been resolved to CTCAE grade 0-1. History of autoimmune diseases (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autologous hemolytic anemia, rheumatoid arthritis, etc.). Patients with known HIV serology positive, hepatitis C infection and/or hepatitis B (Except the patients with positive HepBsAg or core antibody are responding to anti-HBV treatment, they are allowed to participate in the study. Notes: HepBsAg-negative patients at screening, or patients are undergoing treatment with interferon-2a [IFN] or peginterferon-2a [Peg-IFN] and hepatitis B virus [HBV] DNA < 2000 international units [IU], or partients who are receiving nucleoside [acid] analogues at screening and HBV DNA below the lower limit of normal [LLN] are eligible to participate in the study. Pregnancy or breastfeeding during study treatment and follow-up period. Patients with confirmed past history of neurological or psychotic disorders, including epilepsy or dementia. Other serious systemic conditions that may limit the participation in this study (e.g. uncontrolled diabetes, cardiovascular and cerebrovascular disease, severe gastrointestinal disease, and renal disease, etc.).
Facility Information:
Facility Name
The First Affiliated Hospital,Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lingwu Chen
Phone
13302283888
Email
chenlingwu@hotmail.com
First Name & Middle Initial & Last Name & Degree
Lingwu Chen
First Name & Middle Initial & Last Name & Degree
Xugang Dong
Facility Name
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Huang
Phone
13600054833
Email
hjgcp2017@163.com
First Name & Middle Initial & Last Name & Degree
Jian Huang
Facility Name
Peking University Third Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lulin Ma
Phone
13701010872
Email
malulin@medmail.com.cn
First Name & Middle Initial & Last Name & Degree
Lulin Ma
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhuowei Liu
Phone
13610138571
Email
liuzhw@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Zhuowei Liu
Facility Name
The Second Hospital of Tianjin Medical University
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hailong Hu
Phone
13662096232
Email
hhllove2004@163.com
First Name & Middle Initial & Last Name & Degree
Hailong Hu
First Name & Middle Initial & Last Name & Degree
Haitao Wang

12. IPD Sharing Statement

Learn more about this trial

Catumaxomab in Patients With Non-Muscle-Invasive Bladder Cancer Who Have Failed or Are Intolerant to BCG Vaccine

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