Table 4. Ongoing clinical trials combining radiotherapy with checkpoint blockade for patients with melanoma.
| Study Phase | Title | Eligibility (planned patient enrollment) | Treatment Regimen | Sponsor | Registry number |
|---|---|---|---|---|---|
| Pilot | Early Biomarkers of Tumor Response in High Dose Hypofractionated Radiotherapy Word Package 3: Immune Response | Patient requiring hypofractionated radiotherapy (≥3 fractions, ≥9Gy per fraction) with hepatocellular carcinoma or hepatic colorectal cancer lesion; metastatic melanoma or renal cell carcinoma (30) | Collection of blood samples before, during and after radiotherapy | Centre Oscar Lambret | NCT02439008 |
| Pilot | Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiotherapy | Unresectable metastatic melanoma with failed 1 systemic therapy (planned 20; actual = 22) | Ipi (3mg/kg) every 3 weeks for 4 doses; radiation starting 2 days after first dose | Stanford University | NCT01449279 |
| Pilot/I | A Pilot Study of Ipilimumab and Radiation in Poor Prognosis Melanoma | resected or unresected high risk, or recurrent cutaneous or mucosal melanoma | RT+Ipi (no dose specified) | Duke University | NCT01996202 |
| I | A Pilot (Phase 1) Study to Evaluate the Safety and Efficacy of Combination Checkpoint Blockade (Ipi and Nivo) Plus External Beam Radiotherapy in Subjects With Stage IV Melanoma | Unresectable stage IV melanoma with at least 1 radiotherapy amenable lesion; ≥28 days from prior treatment (18) | Concurrent Ipi (3 mg/kg) and Nivo (1 mg/kg) every 3 weeks for 4 doses, followed by Nivo monotherapy (3 mg/kg) every 2 weeks. Radiotherapy (Cohort A: 3Gy × 10, Cohort B: 9Gy × 3) will be initiated between the 1st and 2nd dose of immunotherapy. | Ludwig Institute for Cancer Research | NCT02659540 |
| I | Phase I Study of Ipilimumab Combined With Whole Brain Radiotherapy or Radiosurgery for Melanoma | Metastatic melanoma with brain metastasis (24) | Ipi (dose escalation) every 3 weeks for 4 doses; Arm A: whole-brain radiation first two weeks of Ipi; Arm B: Stereotactic radiosurgery on same day as first dose of ipilimumab | Thomas Jefferson University | NCT01703507 |
| I | Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Fixed Dose Immune Checkpoint Inhibitors in Metastatic Melanoma: Dose Limiting Toxicity and Abscopal Effect | Metastatic melanoma with at least 3 extracranial metastases; ≥28 days from prior treatment (21) | Ipi (3 mg/kg) every 3 weeks for 4 doses (days 1, 22, 43 and 64); Stereotactic radiosurgery (dose escalation: 8Gy × 3, 10Gy × 3, 12Gy × 3) on days 39, 41 and 43 | University Hospital, Ghent | NCT02406183 |
| I | An Exploratory Study to Investigate the Immunomodulatory Activity of Radiotherapy (RT) in Combination With MK-3475 in Patients With Recurrent/Metastatic Head and Neck, Renal Cell Cancer, Melanoma and Lung Cancer | Recurrent head and neck, lung cancer, renal cell carcinoma, skin cancer; stage III or IV renal cell carcinoma; Stage IV lung or cutaneous melanoma (40) | Four arms, two radiation doses (8Gy ×1 v. 5Gy × 4) either preceded by or followed by dose of pembro on the first day of radiation and repeated doses of pembro every 21 days if no progression | Thomas Jefferson University | NCT02318771 |
| IB | A Phase 1b, Open-label, Multicenter, Multidose, Dose-escalation Study of BMS-936558 (MDX-1106) in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Malignant Melanoma | Unresectable stage III or IV melanoma (136) | 8 arms, varying doses and sequence of nivo and ipi in combination or alone | Bristol-Myers Squibb | NCT01024231 |
| I/II | RADVAX: A Stratified Phase I/II Dose Escalation Trial Of Hypofractionated Radiotherapy Followed By Ipilimumab In Metastatic Melanoma | Metastatic melanoma with index lesion between 1 and 5 cm (40; 23 enrolled prior to recruitment cessation) | Stereotactic radiotherapy (dose escalation) followed by ipi (no dose listed) | University of Pennsylvania | NCT01497808 |
| I/II | Phase I/II Trial of Ipilimumab (Immunotherapy) and Hypofractionated Stereotactic Radiotherapy in Patients With Advanced Solid Malignancies | Many solid malignancies with lung or liver metastases; one uveal melanoma (120) | Ipi (3mg/kg) every 21 days for 4 doses with concurrent (days 1-4, cycle 1) or sequential (days 29-33) stereotactic body radiotherapy (12.5Gy × 4, 6Gy × 10) | M.D. Anderson Cancer Center | NCT02239900 |
| II | Concurrent Ipilimumab and Stereotactic Ablative Radiotherapy (SART) for Oligometastatic But Unresectable Melanoma (SART) | Stage III and IV melanoma with 5 or fewer metastatic sites (50) | Ipi (10mg/kg) every 3 weeks for 4 doses, then every 12 weeks; Stereotactic ablative radiotherapy (dose not defined) between 1st and 3rd doses of ipi | Comprehensive Cancer Centers of Nevada | NCT01565837 |
| II | A Phase 2 Study Using Stereotactic Ablative Radiotherapy and Ipilimumab in Patients With Oligometastatic Melanoma | Stage IV melanoma metastatic to <4 sites (30) | Ipi (3 mg/kg) every 3 weeks for 4 doses; Stereotactic radiotherapy at week 5-6; Patients with SD, PR or CR at week 12 may receive additional ipi | Ohio State University Comprehensive Cancer Center | NCT02107755 |
Ipi: ipilimumab; nivo: nivolumab; pembro: pembrolizumab