Investigation of Safety and Tolerability of Catumaxomab in Patients With NMIBC

NCT04819399 | Unknown Phase 1 DMC

• 2 other identifiers: CATUNIBLA2019-002850-22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate the safety, tolerability, and preliminary efficacy of the monoclonal bispecific trifunctional antibody Catumaxomab in patients with non-muscle invasive bladder cancer (NMIBC).

Conditions

Urinary Bladder Neoplasms

Keywords

Non Muscle Invasive Bladder Cancer; NMIBC; Catumaxomab; Intravesical

Outcome Measures

Primary Outcomes (2)

• Dose escalation phase to evaluate DLT incidence

  Dose Limited Toxicity

  approximately 1 year after study start

• Incidence and severity of treatment related adverse events

  Incidence and severity of treatment related adverse events during intravesical instillation with catumaxomab are observed according to NCI CTCAE, Version 5.0

  approximately 2.5 years after study start

Secondary Outcomes (15)

• Anti-drug antibodies (ng/ml)

  approximately 2.5 years after study start

• Cytokines (pg/mL)

  approximately 2.5 years after study start

• Number of EpCAM-positive tumor cells in the urine

  approximately 2.5 years after study start

• Number of immune cells in the urine

  approximately 2.5 years after study start

• Cmax (ng/ml)

  approximately 2.5 years after study start

Study Arms (1)

Catumaxomab

EXPERIMENTAL

intravesical Catumaxomab instillation

Drug: Catumaxomab

Interventions

Catumaxomab DRUG

Procedure: 6 weekly intravesical administration at each dose level; 3 sequential cohorts consisting of 3 patients (part I) 1. cohort 50 µg 2. cohort 70 µg 3. cohort 100 µg Part II will be treated at recommended dose

Catumaxomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be enrolled in this Phase I study only if they meet all of the following criteria:
• Male or non-pregnant, non-breastfeeding female, age 18 years or older at date of consent.
• Any of the following histologically confirmed non-muscle invasive urothelial carcinoma of the bladder:
• High-risk tumors according to EAU guidelines:
• pT1
• G3 HG tumors
• CIS
• Multiple, recurrent and large (\>3cm) pTa G1-G2 LG tumors (all features must be present)
• Patients of the subgroup of highest risk tumours (T1G3/HG associated with concurrent bladder CIS, multiple- and/or large T1G3/HG and/or recurrent T1G3/HG, T1G3/HG with CIS in the prostatic urethra, some forms of variant histology of urothelial carcinoma, lymphovascular invasion) will be only enrolled if they have already failed BCG-treatment or they cannot tolerate it and are ineligible or refuse cystectomy. In the Part II of the study a minimal expression of EpCAM in the tumor tissue may be required, based on preliminary evidence from the Part I of the study
• Previous therapies must be discontinued at least 2 weeks prior to administration of Catumaxomab and all treatment related toxicities must have resolved or decreased to common toxicity criteria (CTCAE) grade 1.
• Time period from primary resection to antibody treatment start must be at least one week and should not exceed 2 weeks.
• Any investigational agent must be discontinued at least 4 weeks or 5 half-lives, whichever is longer, prior to antibody treatment start.
• Female patients of child-bearing potential (for definition refer to section 14.3)must:
• have negative serum pregnancy test prior to study treatment to rule out pregnancy.
• Use at least one method of birth control that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), true sexual abstinence or vasectomized partner from the time of signing the informed consent through 2 weeks after the last study drug treatment.

You may not qualify if:

• Patients will not be enrolled in this Phase I study if they meet any of the following criteria:
• The female patient is pregnant, lactating or breastfeeding or has a positive serum pregnancy test during the screening period.
• Low risk or intermediate risk tumors according to EAU guidelines
• History or signs (obstruction of upper urinary tract or cross hematuria in the ureteral orifice) of urethral or upper tract transitional cell carcinoma (TCC). Patients with T1 disease of the bladder must have no evidence of upper or lower tract disease or a more advanced stage of disease by either computed tomography (CT) urography or magnetic resonance imaging (MRI) urography of the abdomen and pelvis performed within 8 weeks before the first application of study treatment. If intravenous contrast medium for CT and MRI is contraindicated, retrograde ureteropyelography, or CT or MRI without intravenous contras tmedia may be performed.
• Patients with hydronephrosis.
• Any intravesicular or other chemotherapy treatment within 2 weeks or any investigational agent within 4 weeks or 5 half-lives of the agent whatever is longer prior to the initial dose of study drug
• History of recurrent severe urinary tract infections (UTIs) per investigator judgment.
• Active, uncontrolled impairment of the urogenital, renal, hepatobiliary, cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the opinion of the investigator, would predispose the patient to the development of complications from the administration of intravesical therapy.
• A diagnosis of another malignancy within 2 years before the first dose of study treatment, except for superficial skin cancer or localized solid tumors deemed cured by surgery and not treated with systemic anticancer therapy and not expected to require anticancer therapy within the next 2 years i.e., while the patient may be taking study treatment or is in the follow up period of this study.
• Patients with a history of cancer who have completed treatment and are free from disease since at least 5 years can be enrolled.
• Patients with low-risk prostate cancer, e.g.:
• Clinically localized disease (≤T2a) and
• Gleason score ≤6 (3+3) and
• Serum PSA \<10 ng/ml undergoing active surveillance may be enrolled with agreement of the sponsor.
• Patients who cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders).

Sponsors & Collaborators

• Lindis Biotech GmbH: lead

Study Sites (1)

Urologie Planegg

München, Germany

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

catumaxomab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• R Oberneder, MD

  Urologische Klinik München-Planegg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Horst Lindhofer, Dr

CONTACT

498970076624; horst.lindhofer@lindisbiotech.de

Peter Ruf, Dr

CONTACT

4989452396020; peter.ruf@lindisbiotech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 29, 2021
• Study Start: July 7, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2023
• Last Updated: April 5, 2022

Record last verified: 2022-04

Locations

DE (1)