Clinical trial NCT04620239: ENdoluminal LIGHT ActivatED Treatment of Upper Tract Urothelial Cancer (ENLIGHTED) Study
Official title: Multicenter Phase 3 Pivotal Study to Evaluate the Safety and Efficacy of TOOKAD (Padeliporfin) Vascular Targeted Photodynamic Therapy in the Treatment of Low Grade Upper Tract Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Transitional Cell Cancer of Renal Pelvis and Ureter
Keywords: UTUC
Low Grade
Lead sponsor: Steba Biotech S.A.
Sponsor class: OTHER
Collaborators: name: PrimeVigilance
name: ICON plc
First posted: 2020-11-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase III, single arm, non randomized, multicenter trial
Primary purpose: TREATMENT

Brief summary: This is a phase 3, open label, single arm study of padeliporfin in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade non-invasive upper tract urothelial carcinoma in either the kidney or the ureter. Patients will be treated with padeliporfin VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for up to an additional 48 months in the long term (non intervention) follow up phase with the specific duration depending on the patient's response to treatment

Detailed description: Induction Treament Phase: Patients entered in the study will undergo an induction treatment phase consisting of 1-3 padeliporfin VTP treatments provided 4 weeks (28 +/-3 days) apart. The goal of this induction treatment phase will be to achieve Complete Response (CR) in the involved ipsilateral tract system. During this phase, patients will be treated with padeliporfin VTP to visually identified tumor sites in the calyces, renal pelvis and/or ureter and subsequently examined endoscopically at 28 +/- 3 days post treatment to determine whether the treatment was successful. If CR is not achieved, an additional two treatments of padeliporfin VTP are permitted 28 +/- 3 days apart for a total of up to 3 treatments during the induction treatment phase. The Primary Response Evaluation (PRE) will be performed 28 +/- 3 days after the last VTP treatment, to determine if the treatment was successful at achieving CR defined as: absence of visible tumor on endoscopy, negative urinary cytology by instrumented collection, and no evidence of tumor on biopsy (if feasible). Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR. If CR is not achieved after 3 treatments with padeliporfin VTP the treatment will be considered unsuccessful and the patient will be discontinued from the Treatment Phases.

Maintenance Treatment Phase: Patients achieving CR at the induction treatment phase will be allowed into the maintenance treatment phase of the study. The patients will then be followed over a period of 12 months post PRE, to assess the duration of response and its safety, and to provide planned maintenance treatment.

Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable as defined by the following criteria: low-grade tumors with the largest tumor (index tumor) betwen 5 mm and 15 mm in diameter, in up to 2 anatomical locations in the calyces, renal pelvis or the ureter with ureter involvement in one anatomical location with no more than 20 mm of contiguous ureteral length). Patients with treatable tumor recurrence post Induction Treatment Phase would be considered as no longer having 'complete response in the entire ipsilateral kidney' and time to recurrence will be recorded. Patients undergoing extirpative surgery of any part of the ipsilateral kidney or ureter for indications related to urothelial cancer will be considered as no longer having CR and time to this event will be recorded.

Long Term Follow-up Phase: Patients completing the 12 months of the maintenance treatment phase of the study, could be followed for an additional 48 months to monitor for disease related outcomes and VTP treatment related adverse events with the specific duration depending on the patient's response to treatment. No additional padeliporfin VTP treatment will be administered during this phase. Patients completing the maintenance phase of the study who are in CR in V3 will undergo additional assessments 18 and 24 months (+/- 1 month) post-PRE and annually thereafter and for up to 5 years post PRE or until recurrence, progression, death or loss to follow up, to document safety and ongoing response.

Eligibility criteria: Inclusion Criteria:

* Male and female patients 18 years or older
* Able to understand and provide written informed consent and willing to comply with all tests and procedures associated with the study
* New or recurrent low-grade, non-invasive UTUC disease
* Biopsy-proven disease . A concurrence of the central pathology reader will be required for eligibility.
* Up to 2 biopsy-proven sites of low-grade involvement with the largest tumor (index tumor) between 5 mm and 15 mm in diameter (as measured by endoscopy), both located in the calyces,renal pelvis or in the ureter of the ipsilateral kidney, with an absence of high-grade cells on cytology. (Ureter involvement should be in one anatomical location with no more than 20 mm of contiguous ureteral length)
* Karnofsky Performance Status ≥ 50%
* Adequate organ function defined at baseline as:

  * ANC ≥1,000/ μl,
  * Platelets ≥75,000/ μl, Hb ≥9 g/dl,
  * INR ≤ 2
  * Estimated glomerular giltration rate (eGFR) ≥30 ml/min (using CKD-EPI Method)
  * Total serum bilirubin \<3 mg/dL, AST/ALT ≤5× upper limit of normal

Exclusion Criteria:

* Current high-grade or muscle invasive (\>pT1) urothelial carcinoma of the bladder
* Carcinoma in situ (CIS) current or previous in the upper urinary tract
* History of invasive T2 or higher urothelial cancer in past 2 years
* Participation in another clinical study involving an investigational product within 1 month before study entry
* BCG or local chemotherapy treatment (including VEGF-targeted therapy) in the upper urinary tract within 2 months prior to inclusion
* Systemic chemotherapy treatment (including VEGF-targeted therapy) within 2 months prior to enrollment
* Prohibited medication that could not be adjusted or discontinued prior to study treatment

  • Patients with photosensitive skin diseases or porphyria
* Any other medical or psychiatric co-morbidities, including decompensated heart failure, unstable angina or coronary artery disease or severe pulmonary or liver disease or current heavy smoker that, in the opinion of the study investigator, would make the patient a poor candidate for the study
* Pregnant or breast-feeding women.Women of childbearing potential (WOCBP) must undergo a negative serum pregnancy test prior to study entry.
* Men and women of reproductive potential not willing to observe conventional and effective birth control for the duration of treatment and for 90 days following the last padeliporfin VTP treatment.

Primary outcomes:
measure: Number of patients with absence of UTUC tumors in the entire ipsilateral calyces, renal pelvis and ureter
timeFrame: 28 +/- 3 days post last treatment
Secondary outcomes:
measure: Duration of response at the entire ipsilateral kidney
timeFrame: 12 months post PRE
measure: Duration of response at the entire ipsilateral kidney
timeFrame: 3, 6, 9 months post PRE
measure: Duration of response at the Treatment Area of the ipsilateral kidney
timeFrame: 3, 6, 9, and 12 months post PRE
measure: Overall renal function
timeFrame: 6 and 12 months post PRE
measure: Kidney organ loss or preservation
timeFrame: 3, 6, 9, and 12 months post PRE
measure: Pathological evaluation of response
timeFrame: After at least one VTP treatment
measure: Patients with ureteral obstruction and/or ureteral stent
timeFrame: Baseline 12 months
measure: Long Term follow-up Duration of the response
timeFrame: 18, 24,36,48 and 60 months post PRE or 6 and 12 months post PRE
measure: Long Term follow-up Kidney organ loss or preservation
timeFrame: 18, 24,36,48 and 60 months post PRE or 6 and 12 months post PRE
measure: Long Term follow-up Overall renal functional
timeFrame: 18, 24,36,48 and 60 months post PRE or 6 and 12 months post PRE
measure: Long Term follow-up Safety Follow up
timeFrame: 18, 24,36,48 and 60 months post PRE or 6 and 12 months post PRE
measure: Exploratory Endpoint
timeFrame: Baseline
measure: Pharmacokinetic Endpoint Cmax
timeFrame: 0 (before injection) and 20, 40, 60, 90, 120 and 360 mn after end of injection
measure: Pharmacokinetic Endpoint Tmax
timeFrame: 0 (before injection) and 20, 40, 60, 90, 120 and 360 mn after end of injection
measure: Pharmacokinetic Endpoint T1/2
timeFrame: 0 (before injection) and 20, 40, 60, 90, 120 and 360 mn after end of injection
measure: Pharmacokinetic Endpoint AUC
timeFrame: 0 (before injection) and 20, 40, 60, 90, 120 and 360 mn after end of injection
measure: Pharmacokinetic Endpoint CL
timeFrame: 0 (before injection) and 20, 40, 60, 90, 120 and 360 mn after end of injection
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California - Irvine Medical Center
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine at USC Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital, The Sidney Kimmel Cancer Center
state: Maryland
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University (OSU)
state: Ohio
city: Hershey
country: United States
facility: The Pennsylvania State University (Penn State) Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Linz
country: Austria
facility: Urologie und Andrologie Ordensklinikum Linz GmbH Elisabethinen
city: Lille
country: France
facility: CHU de Lille - Hopital Claude Huriez
city: Lyon
country: France
facility: HCL Hopital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Rouen
country: France
facility: CHU de Rouen - Hopital Charles-Nicolle
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Coruña
country: Spain
facility: Hospital Universitario de A Coruña
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
Study officials:
affiliation: UT Southwestern Medical Center
name: Vitaly Margulis, MD
role: PRINCIPAL_INVESTIGATOR
References: