NCT01838200

Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma

A Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) and Followed by Ipilimumab Therapy in Patients With Advanced Metastatic Melanoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase 1, open-label, dose-escalation, single-center study in patients with histologically confirmed Stage III or IV melanoma and at least 3 metastatic cutaneous or subcutaneous lesions that were suitable and accessible for intralesional (IL) injection (1 lesion), biopsy (1 lesion), and response evaluation (1 lesion). The primary objective was to determine the safety of IL administration of bacillus Calmette-Guerin (BCG) followed by oral dosing with an antibiotic (isoniazid) and intravenous (IV) infusions of ipilimumab. Secondary objectives were to evaluate the clinical efficacy (induction of tumor response) and immunogenicity (induction of immune response against the tumors) of the combination regimen.

Detailed description

Patients were enrolled into one of two study cohorts depending on the induration noted after a baseline purified protein derivative (PPD) skin test to determine tuberculin reactivity. Cohort 1 comprised patients with an induration of \<10mm in diameter, and Cohort 2 comprised patients with an induration of ≥10mm. Enrollment was staggered by 3 weeks for each of the first 3 patients in Cohort 1, Group 1 to enable safety monitoring of each patient prior to exposure of additional patients. In all cohorts, study treatment included BCG (200 µL volume) given IL on Day 1, isoniazid (300 mg) given orally daily from Days 29 to 56, and ipilimumab (3 mg/kg) given IV every 3 weeks (± 3 days) on Days 36, 57, 78, and 99. The dose of BCG varied by assigned treatment group: Cohort 1, Group 1 received 0.16 - 0.64 × 10\^6 colony-forming units (CFU); Cohort 1, Group 2 received 0.8 - 3.2 x 10\^6 CFU; Cohort 1, Group 3 was to receive 4.0 - 16.0 x 10\^6 CFU; and Cohort 2 was to receive 0.16 - 0.64 × 10\^6 CFU. Enrollment into Cohort 2 was to be initiated after the final patient in Cohort 1, Group 1 reached Week 7. Enrollment was then to proceed in parallel for Cohort 2 and Cohort 1, Groups 2 and 3. Patients were monitored for safety, tumor response, and immunogenicity (cellular, humoral, and in situ immunity) for the duration of study participation.

Conditions

• Metastatic Melanoma

Interventions

Type	Name	Description
BIOLOGICAL	Bacillus Calmette-Guérin (BCG) vaccine	BCG was to be administered as a single intralesional injection (200 µL volume) on Day 1 at varying doses depending on cohort assignment.
DRUG	Ipilimumab	Ipilimumab was to be administered as a 90-minute IV infusion at a dose of 3 mg/kg every 3 weeks (± 3 days) on Days 36, 57, 78, and 99.
DRUG	Isoniazid	Isoniazid was to be administered orally at a dose of 300 mg (3 × 100 mg tablets) every day from Days 29 through 56.

Timeline

• Start date: 2014-03-01
• Primary completion: 2015-08-17
• Completion: 2015-08-17
• First posted: 2013-04-23
• Last updated: 2022-10-12
• Results posted: 2019-03-28

Locations

1 site across 1 country: Australia