Clinical trial NCT02821182: A Phase II Trial of Stereotactic Body Radiotherapy With Concurrent Anti-PD1 Treatment in Metastatic Melanoma.
Official title: A Phase II Trial of Stereotactic Body Radiotherapy With Concurrent Anti-PD1 Treatment in Metastatic Melanoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: GZA Ziekenhuizen Campus Sint-Augustinus
First posted: 2016-07-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: We hypothesize that combining anti-PD1 treatment with radiotherapy might result in improved clinical response rates and PFS compared to anti-PD1 treatment in monotherapy.

The current phase II trial aims at exploring the suggested benefits of the combination and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD1 treatment.


Eligibility criteria: Inclusion Criteria:

* Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
* Histologically confirmed diagnosis of melanoma
* At least 3 extracranial measurable metastatic lesions per RECIST v1.1. All radiology studies must be performed within 28 days prior to registration
* First line anti-PD1 treatment.
* Karnofsky Performance status \> 60
* Age 18 years or older
* Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
* Female participants who are breastfeeding or plan to breastfeed should be instructed to discontinue nursing during treatment.
* Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study treatment
* Demonstrate adequate organ function defined as the following:

  * AST and ALT ≤2.5 X ULN or ≤5 X ULN with liver metastases
  * Serum total bilirubin ≤1.5 X ULN or direct bilirubin ≤ULN for patient with total bilirubin level \>1.5 ULN
  * Serum creatinine ≤1.5 X ULN
  * Absolute neutrophil count \>1,000 /mcL
  * Platelets \>75,000 /mcL
  * Hemoglobin \>9 g/dL or \> 5.6 mmol/L
* No history of active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents
* Prior malignancy: Subjects who have had another malignancy should be disease-free for 5 years, or should have a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma
* No evidence of interstitial lung disease
* No uncontrolled central nervous metastases and/or carcinomatous meningitis.
* No prior radiotherapy interfering with SBRT.
* No concomitant therapy with IL-2, interferon, other immunotherapy regimens, chemotherapy, immunosuppressive agent or chronic use of systemic corticosteroids.
* No active infection requiring systemic therapy
* No known history of human immunodeficiency virus (HIV)
* No known active Hepatitis B or Hepatitis C
* Did not receive a live vaccine within 30 days prior to start of study treatment
* No mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
* Patient not unlikely to comply with the protocol; i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study

Primary outcomes:
measure: Efficacy
timeFrame: 12 weeks
Secondary outcomes:
measure: Immunologic responses
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospital Ghent
state: West Vlaanderen
Study officials:
References:
citation: De Wolf K, Kruse V, Sundahl N, van Gele M, Chevolet I, Speeckaert R, Brochez L, Ost P. A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response. J Transl Med. 2017 Jan 31;15(1):21. doi: 10.1186/s12967-017-1123-x.