A study for evaluating investigational drug IMMU-132 in treatment of malignant urothelial cancers, in patients with failures in previous treatments with platinum-based regimens or Anti-PD-1/PD-L1-based immunotherapy.
- Conditions
- Histologically documented locally advanced (tumor [T] 4b, any node [N]or any T, N 2-3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract predominantMedDRA version: 20.0Level: LLTClassification code 10077840Term: Urothelial cancer of renal pelvisSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046723Term: Urothelial carcinoma ureterSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10046728Term: Urothelial carcinoma urethraSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001167-23-FR
- Lead Sponsor
- Immunomedics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
1. Female or male subjects, >18 years of age, able to understand and give written informed consent.
2. Subjects with histologically documented locally advanced (tumor [T] 4b, any node [N]; or any T, N 2-3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract predominant
3. ECOG Performance status score of 0 or 1.
4. Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
a) Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
b) Or received adjuvant platinum-containing therapy following cystectomy for localized muscle-invasive urothelial cancer, with recurrence/progression =12 months following completion of therapy.
5. Cohort 1: In addition to criterion #4, have had progression or recurrence of urothelial cancer following receipt of an anti-PD-1 /PD-L1 therapy and have a creatinine clearance = 60 ml/min.
6. Cohort 2: Were ineligible for cisplatin-based therapy* for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy and have a creatinine clearance between 30-60mL/min.
* Cisplatin ineligible defined as meeting one of the following criteria:
a. Creatinine Clearance <60 ml/min
b. Grade >=2 audiometric hearing loss
c. Grade >=2 peripheral neuropathy
d. New York Heart Association Class III heart failure
7. Adequate hematology without transfusion support (Hemoglobin > 9 g/dL, Absolute Neutrophil Count > 1,500 per mm3, and Platelets > 100,000 per mcL).
8. Adequate hepatic function (Bilirubin = 1.5 IULN, AST and ALT = 2.5 x IULN or = 5 x IULN if known liver metastases and serum albumin >3 g/dl)).
9. Subjects must have a 3-month life expectancy.
10. Adequate coagulation (Prothrombin Time (PT) or INR and Activated Partial Thromboplastin Time (aPTT) =1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
11. Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
13. Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >2 years.
14. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
1. Women who are pregnant or lactating.
2. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to the first dose of trial treatment.
3. Has a diagnosis of immunodeficiency.
4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1) from adverse events due to agents administered more than 4 weeks earlier.
5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 from adverse events due to a previously administered agent.
? Note: Subjects with = Grade 2 neuropathy or = Grade 2 alopecia are an exception to this criterion and may qualify for the study.
? Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
6. Requires concomitant medication interfering with ABCA1 transporter or UGT1A1
7. Subjects with Gilbert’s disease.
8. Patients who previously received irinotecan.
9. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Gleason score = 6, PSA undetectable.
10. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. All patients with carcinomatous meningitis are excluded regardless of clinical stability.
11. Has active cardiac disease, defined as:
o Myocardial infarction or unstable angina pectoris within 6 months of the first date of study therapy.
o History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
o New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of < 40%.
12. Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) and subjects with a history of bowel obstruction.
13. Has prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of enrollment.
14. Must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids = 20 mg prednisone or equivalent daily are permitted for reasons outside of CNS disease provided the dose is stable for 4 weeks).
15. Has an active infection requiring systemic therapy.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV -1/2 antibodies)
17. Has known active Hepatitis B or Hepatitis C (In patients with a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method