NCT01970527

RADVAX: A Stratified Phase II Dose Escalation Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Metastatic Melanoma

Terminated Phase 2 Results posted Last updated 31 January 2020

What this trial tests

Phase 2 trial testing Ipilimumab in Recurrent Melanoma in 23 participants. Terminated before completion.

Timeline

1 March 2014

Primary endpoint
3 November 2018

21 June 2019

Quick facts

Lead sponsor	University of Washington
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	23
Start date	1 March 2014
Primary completion	3 November 2018
Estimated completion	21 June 2019
Sites	1 location across United States

Drugs / interventions tested

• Ipilimumab — full drug profile →
• Laboratory Biomarker Analysis — full drug profile →
• Pharmacological Study — full drug profile →
• Stereotactic Body Radiation Therapy — full drug profile →

Conditions studied

• Recurrent Melanoma — all drugs for Recurrent Melanoma →
• Stage IV Skin Melanoma — all drugs for Stage IV Skin Melanoma →

Sponsor

University of Washington

Who can join

18 and older, any sex, with Recurrent Melanoma or Stage IV Skin Melanoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Immune-related Clinical Response, Defined as Proportion of Patients Treated at the Maximum-tolerated Dose (MTD) Who Achieve Either a Complete or Partial Immune-related Response
  Time frame: Up to 60 days after last ipilimumab injection
  Scored on a non-index lesion using immune-related response criteria according to immune-related Response Evaluation Criteria in Solid Tumors version 1.1. The number of immune-related responses will be tabled by stratum and SBRT fraction dose level. At the MTD, the immune-related response rate and 95% exact confidence interval will be estimated separately for previously untreated and previously tre
• Immune-related Progression-free Survival (irPFS)
  Time frame: Time from first day of radiotherapy to first documented immune-related progressive disease, death due to any cause or last patient contact alive and progression-free, assessed at 6 months
  irPFS will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.. For some patients no scans were available for irRECIST reads, in which case change of management was determined to be the point of progression.
• Late Toxicities, Graded According to the Radiation Therapy Oncology Group/European Organization for Research, the Treatment of Cancer Late Morbidity Scoring System, and the Common Terminology Criteria for Adverse Events Version 4.0
  Time frame: Up to 3 years
  Defined generally as an adverse event associated with the treatment which occurs beyond 30 days after last injection (i.e., adverse events which are observed months after treatment are most likely associated with SBRT). All dose-limiting toxicities and late toxicities will be graded and tabled by lesion site stratum and SBRT fraction dose level. Toxicity attribution to either SBRT or ipilimumab wi
• Overall Survival
  Time frame: Time from first day of radiotherapy to death due to any cause or last patient contact alive, assessed at 12 months
  Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.

Sponsor's own description

This phase II trial studies how well stereotactic body radiotherapy and ipilimumab work in treating patients with stage IV melanoma. Stereotactic body radiotherapy (SBRT) may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Monoclonal antibodies, such as ipilimumab, target certain cells to interfere with the ability of tumor cells to grow and spread. Giving SBRT with ipilimumab may kill more tumor cells.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors.
   Liu Y, Dong Y, Kong L, Shi F, et al · · 2018 · cited 337× · PMID 30115069 · DOI 10.1186/s13045-018-0647-8
2. Current clinical trials testing the combination of immunotherapy with radiotherapy.
   Kang J, Demaria S, Formenti S. · · 2016 · cited 293× · PMID 27660705 · DOI 10.1186/s40425-016-0156-7
3. Combinations of immunotherapy and radiation in cancer therapy.
   Vatner RE, Cooper BT, Vanpouille-Box C, Demaria S, et al · · 2014 · cited 189× · PMID 25506582 · DOI 10.3389/fonc.2014.00325
4. Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma.
   Barsoumian HB, Ramapriyan R, Younes AI, Caetano MS, et al · · 2020 · cited 166× · PMID 33106386 · DOI 10.1136/jitc-2020-000537
5. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment.
   Vanpouille-Box C, Pilones KA, Wennerberg E, Formenti SC, et al · · 2015 · cited 138× · PMID 26148880 · DOI 10.1016/j.vaccine.2015.05.105
6. Current Advances in the Treatment of BRAF-Mutant Melanoma.
   Patel H, Yacoub N, Mishra R, White A, et al · · 2020 · cited 133× · PMID 32092958 · DOI 10.3390/cancers12020482
7. Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade.
   Buchbinder E, Hodi FS. · · 2015 · cited 130× · PMID 26325034 · DOI 10.1172/jci80012
8. Combinatorial approach to cancer immunotherapy: strength in numbers.
   Vilgelm AE, Johnson DB, Richmond A. · · 2016 · cited 83× · PMID 27256570 · DOI 10.1189/jlb.5ri0116-013rr