Phase II non randomized clinical trial of NIVOLUMAB/IPILIMUMAB maintenance following first-line chemotherapy in unresectable locally advanced or metastatic urothelial cancer (SOGUG-VEXILLUM)

Phase 1

• Conditions: nresectable locally advanced or metastatic urothelial cancer; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2024-514293-46-00
• Lead Sponsor: Grupo Espanol De Oncologia Genitourinaria-Socug

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-05
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Male or female subjects = 18 years old., Only patients without progressive disease as per RECIST v1.1 guidelines after 4-6 cycles of chemotherapy will be allowed to be included. Baseline CT scan before inclusion should confirm that patients are on CR, PR or SD according to RECIST 1.1 criteria., Tumor tissue (formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition) must be available at baseline., Willingness and ability of patients to comply with the protocol for the duration of the study including undergoing treatment as well as availability for scheduled visits and examinations including follow up., Patients with adequate normal organ and marrow function as defined below: a) Haemoglobin = 9.0 g/dL. b) Absolute neutrophil count (ANC) > 1500 per mm 3. c) Platelet count = 100,000 per mm 3. d) Serum bilirubin = 1.5 X institutional upper limit of normal (ULN) unless liver metastases are present, in which case it must be = 2X ULN. This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology); however, they will be allowed only in consultation with their physician. e) Serum transaminases (ALT, AST and GGT) = 2.5X institutional upper limit of normal unless liver metastases are present, in which case it must be = 3X ULN. f) Measured creatinine clearance (CL) > 30 mL/min or Calculated creatinine CL > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for the determination of creatinine clearance (For more information see page 13 of the protocol), Female subjects of childbearing potential (WOCBP) must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%; refer to ANNEX III) for the duration of the study treatment and for 5 months after the last dose of study treatment. A woman is considered of childbearing potential ( i.e. fertile) following menarche and until becoming post-menopausal unless permanently sterile. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: a) Amenorrheic for =1 year in the absence of chemotherapy and/or hormonal treatments b) Luteinizing hormone (LH) and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range c) Radiation induced oophorectomy with last menses >1 year ago d) Chemotherapy induced menopause with >1 year interval since last menses e) Surgical sterilization (bilateral oophorectomy or hysterectomy) f) Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) g) Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)., Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities., Eastern Cooper

Exclusion Criteria

ECOG performance status of >1 (Karnofsky < 70%)., Subjects that have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior to the first dose of trial treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid)., Active or prior documented autoimmune disease within the past 2 years which requires systemic therapy. Note: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Subjects with Type I diabetes mellitus are not excluded., Active or prior documented inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis)., Inadequate haematological/organ function., Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism., Persistence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that have not resolved to Grade 1 (NCI-CTCAE v5.0) or baseline before administration of study treatment., Active hepatitis B virus or hepatitis C virus., Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines (i.e. SARS-CoV-2 and Influenza vaccines will be permitted)., Patients who have a known secondary malignancy that is progressing or has required active treatment within the past 2 years. Note: Patients with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are eligible, Pregnant or lactating females. Fertile and sexually active patients that are not willing to use the appropriate highly effective contraceptive methods., Patients whose disease progressed by RECIST v1.1 on or after first-line chemotherapy for urothelial cancer in the advanced or metastatic setting., Any underlying medical or psychiatric disorder, which, in the opinion of the investigator, makes the administration of ipilimumab and nivolumab unsafe or interferes with the informed consent process or trial procedures., Participation in other studies involving investigational drug(s) within 4 weeks prior to inclusion. Observational studies are permitted., Prior immunotherapy with IL-2, IFN-a or treatment with any immune checkpoint inhibitor therapy (e.g, CTLA4, PD-1, or PD-L1 targeting agent) for the unresectable metastatic setting. Note: Patients may have received immunotherapy in the adjuvant setting as long as the last dose of adjuvancy was administered at least 12 months prior to the first dose of trial treatment., Receipt of any type of systemic chemotherapy or anticancer therapy within 3 weeks before starting treatment., Previously identified allergy or hypersensitivity to components of the study treatment formulations., History of allogeneic organ transplant., Any non-cancer treatment with vaccines used for the prevention of infectious diseases (up to 1 month before or after any dose of ipilimumab and nivolumab)., Major surgery (i.e. cystectomy) less than 28 days prior to the first dose of study treatment., Patients with known symptomatic cent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified