NCT02659540

Pilot Study of the Safety/Efficacy of Combination Checkpoint Blockade + External Beam Radiotherapy in Stage IV Melanoma

A Pilot (Phase 1) Study to Evaluate the Safety and Efficacy of Combination Checkpoint Blockade (Ipilimumab and Nivolumab) Plus External Beam Radiotherapy in Subjects With Stage IV Melanoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an ongoing, Phase 1, open-label, multicenter, pilot study of the checkpoint antibodies ipilimumab and nivolumab in combination with radiotherapy (RT) in 18 subjects with unresectable Stage IV melanoma. The primary study objective is to evaluate the safety of study treatment. Secondary objectives are to evaluate objective response rate (ORR) and disease control rate (DCR) at Weeks 12 and 18, duration of response, progression-free survival (PFS), and overall survival (OS).

Detailed description

All subjects received concurrent ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks for 4 doses (i.e., Weeks 1, 4, 7 and 10), followed by nivolumab monotherapy administered at a dose of 240 mg every 2 weeks through Week 18. Continued nivolumab monotherapy was permitted beyond Week 18 at the Investigator's discretion as either 240 mg every 2 weeks or 480 mg every 4 weeks starting at Week 20. Extracranial RT was initiated after the first dose and before the second dose of immunotherapy, with RT dosing administered to a target lesion as follows: * Cohort A: conventional total palliative dose of 30 Gy delivered over 2 weeks in 10 fractions of 3 Gy each; * Cohort B: hypofractionated high-dose of 27 Gy delivered over 2 weeks in 3 fractions of 9 Gy each. Eligible subjects were initially enrolled into Cohort A. After 9 evaluable subjects completed at least the first 2 cycles of concurrent ipilimumab and nivolumab treatment, a safety review was performed and determined that the safety of Cohort A was acceptable based on a protocol-specified tolerability threshold of ≤ 7 of 9 subjects experiencing Grade 3 or 4 drug- or radiation-related adverse events (AEs), where Grade 3 or 4 amylase or lipase abnormalities that were not associated with clinical symptoms were not included in the safety assessment. Additional subjects were then accrued to Cohort B. Subjects were followed on study for 100 days after the last study drug administration. Post-study follow-up, which occurs at least every 12 (± 1) weeks for 3 years after completion of the 100-day on-study follow-up, is still being performed for some patients .

Conditions

• Melanoma

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab was administered as an intravenous (IV) infusion over approximately 30 or 90 minutes, with dosing calculated using body weight.
DRUG	Ipilimumab	Ipilimumab was administered as an IV infusion over approximately 30 or 90 minutes, with dosing calculated using body weight. The ipilimumab infusion was initiated approximately 30 minutes after the end of the nivolumab infusion on applicable dosing days.
RADIATION	Radiotherapy	RT was delivered in accordance with cohort assignment and institutional practices.

Timeline

• Start date: 2016-10-13
• Primary completion: 2019-05-09
• Completion: 2020-07-27
• First posted: 2016-01-20
• Last updated: 2022-10-28
• Results posted: 2020-01-02

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study