PK Sub-Study of QUILT-3.032 (CA ALT-803-01-16) and of QUILT-2.005 (CA ALT-803-01-14)

Pharmacokinetics Clinical Trial

Official title:

A Pharmacokinetic Sub-Study of QUILT-3.032 (CA ALT-803-01-16): A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer and QUILT-2.005: A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04142359
• Other study ID #: QUILT-3.032-2.005-PK
• Status: Terminated
• Start date: October 11, 2019
• Est. completion date: April 6, 2020

Study information

• Verified date: January 2021
• Source: Altor BioScience
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Non-interventional PK sub-study of QUILT-3.032 (CA-ALT-803-01-16) and QUILT-2.005 (CA-ALT-803-01-14)

Description:

QUILT-3.032 is a Phase 2, open-label, single-arm, three-cohort, multicenter study of intravesical BCG plus ALT-803 in patients with BCG unresponsive high grade NMIBC. Patients will be enrolled into one of three study cohorts. Cohort A will enroll 80 patients who have histologically confirmed presence of BCG-unresponsive carcinoma in situ (CIS) [with or without Ta or T1 disease]. Cohort B will enroll 80 patients who have histologically confirmed BCG-unresponsive high-grade Ta or T1 disease. Cohort C will enroll up to 23 patients who also have histologically confirmed presence of BCG-unresponsive CIS [with or without Ta/T1 papillary disease]. Patients in Cohorts A and B will receive ALT-803 plus BCG combination treatment. Patients in Cohort C will receive ALT-803 alone. Enrollment of Cohort C will start once the enrollment of Cohort A is complete. Cohorts A, B, and C are independent study cohorts and will be separately evaluated for efficacy. All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus ALT-803 or ALT-803 alone weekly for 6 consecutive weeks during the induction treatment period.

QUILT-2.005 is a phase 2b, randomized, two-cohort, open-label, multicenter study of intravesical ALT-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC. Patients will be enrolled into one of two study cohorts and randomized into two arms to be treated with either ALT-803 plus BCG or BCG alone. Cohort A will initially enroll 366 patients who have histologically confirmed CIS (with or without Ta/T1 papillary disease). Cohort B will initially enroll 230 patients who have histologically confirmed high-grade papillary Ta/T1 disease only. Cohorts A and B are two independent study cohorts and will be evaluated separately for efficacy.

PK sub-study: Blood samples to determine serum levels of ALT-803 will be collected on study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. Six subjects from either cohort A (either study) or cohort C (QUILT 3.032) and six subjects from cohort B (either study) will be sampled initially. Up to an additional 4 subjects for each cohort may also be sampled. Patients enrolled in QUILT 2.005 must have been randomized to receive ALT-803 plus BCG to be eligible for the PK sub-study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: April 6, 2020
• Est. primary completion date: April 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Only subjects who are eligible for and have entered into protocol QUILT-3.032 or QUILT-2.005 may participate in this sub-study.

• Patients enrolled in QUILT-2.005 must have been randomized to receive ALT-803 plus BCG to participate in this sub-study.

Exclusion Criteria:

• Refusal to provide voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.

• Loss of = 475 mL blood volume or blood transfusion of any blood product within 3 months prior to screening.

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Biological:
• BCG in Combination with N-803
BCG in Combination with N-803

Drug:
• N-803 alone
N-803 alone

Locations

Country	Name	City	State
United States	NYU Winthrop University Hospital Department of Urology	Garden City	New York
United States	UCLA Department of Urology	Los Angeles	California
United States	University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Manhattan Medical Research	New York	New York
United States	Adult & Pediatric Urology	Omaha	Nebraska
United States	Virginia Urology	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Altor BioScience

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PK Parameter	Half-life (t½)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Apparent (extravascular) volume of distribution (Vz/F)	Study day 1 prior to dosing, and at post-bladder voiding (+15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Apparent (extravascular) clearance (CL/F)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Maximum observed concentration (Cmax)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Time of the observed maximum concentration (Tmax)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Primary	PK Parameter	Area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf)	Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.