MelanomaPhase 1NCT02406183
Trial of SBRT With Concurrent Ipilimumab in Metastatic Melanoma
A Phase 1 study testing Stereotactic body radiotherapy (SBRT) and Ipilimumab in people with Melanoma and Effects of Immunotherapy, run by Radiotherapie at 1 site in Belgium.
Trial summary
The prognosis of advanced metastatic melanoma remains poor although a breakthrough has been achieved with the novel anti-CTLA-4 treatment (ipilimumab) for a subset of patients. Unfortunately, due to immune resistance, the majority of patients do not obtain long-lasting clinical benefit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Effects of Immunotherapy, Adverse Effect of Radiation Therapy
- What is being tested?
- Stereotactic body radiotherapy (SBRT) and Ipilimumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteBelgium
- Study dates
- Mar 2015to Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent and willingness to comply to the treatment and follow-up
- Histological diagnosis of melanoma,
- at least 3 extracranial measurable metastatic lesions per RECIST 1.1,
- Karnofsky Performance score >60,
- Age ≥18,
- Life expectancy ≥ 16 weeks
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- Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment. Men and women should agree to use effective contraception, during the study and for 1 month following the last dose of investigational product.
- ≥ 28 days between last treatment with standard or experimental chemotherapy, surgery, radiotherapy, cytokine therapy or immunotherapy. Patient should be completely recuperated of any clinical toxicity developed during previous treatments.
- Patients should have adequate organ function for ipilimumab treatment
Who cannot join
- Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants.
- Prior malignancy: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- Prior radiotherapy preventing treatment with SBRT.
- Disorder precluding understanding of trial information.
- Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
- Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C.
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- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses).
- Pregnant women
- Breast feeding
- History of or current immunodeficiency disease or prior treatment compromising immune function, prior allogeneic stem cell transplantation.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Dept. of Radiotherapy, Ghent University Hospital
Ghent, Oost-Vlaanderen, 9000
About this study
Official title: Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Fixed Dose Immune Checkpoint Inhibitors in Metastatic Melanoma: Dose Limiting Toxicity and Abscopal Effect
The prognosis of advanced metastatic melanoma remains poor although a breakthrough has been achieved with the novel anti-CTLA-4 treatment (ipilimumab) for a subset of patients. Unfortunately, due to immune resistance, the majority of patients do not obtain long-lasting clinical benefit. Radiotherapy is able to interfere with immune resistance by inducing immunogenic cell death. Preclinical evidence indicates that combining radiotherapy with anti-CTLA-4 treatment increases response rates compared to single agent treatment. These data are supported by several spectacular clinical cases and one retrospective study. The investigators hypothesize that combining ipilimumab with radiotherapy will result in a higher response rate compared to ipilimumab or radiotherapy in monotherapy. Given the complexity of the interaction in anti-tumor immunity, the first goal of this project is to assess the safety of the combined treatment.
Read the detailed description
The safety profiles of ipilimumab and SBRT are well studied separately 22-24, but prospective data on the combination of ipilimumab and high-dose SBRT are lacking. Consequently, the first goal of the proposed prospective phase I trial is to assess the safety (dose limiting toxicity, DLT) of the combination of high-dose SBRT and ipilimumab in patients with advanced melanoma.
- Being tested
- Stereotactic body radiotherapy (SBRT), Ipilimumab
- Medical subject headings
- Melanoma, Radiation Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic body radiotherapy (SBRT)Radiation
Also called SABR
The SBRT dose will be escalated in 3 steps as described above and will be given on d39, d41 and d43
IpilimumabDrug
Also called Yervoy
Ipilimumab 3mg/kg will be given IV on d1, d22, d43 and d64
| Study group | Role | What they receive |
|---|---|---|
| Treatment (SBRT, Ipilimumab) | Experimental | Drug: Ipilimumab Dosage: Ipilimumab will be administered intravenously at 3 mg/kg every 3 weeks for 4 cycles,
Radiation: Stereotactic Body Radiotherapy Radiation therapy 24 Grays in 8 Grays fractions, Radiation therapy 30 Grays in 10 Grays fractions, Radiation therapy 36 Grays in 12 Grays fractions Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MDT) that is associated with dose-limiting toxicity (DLT) in 25% of patients.
Measured: 2 years
Secondary outcomes (7)
Preliminary anti-tumor activity following escalating doses of radiation combined to ipilimumab using the immune related response criteria irRC
Measured: 2 years
Overall survival
Measured: 2 years
Progression-free survival
Measured: 2 years
Immunomonitoring (absolute lymphocyte count)
absolute lymphocyte count
Measured: 2 years
Immunomonitoring (frequencies of Foxp3+ Treg-cells)
frequencies of Foxp3+ Treg-cells
Measured: 2 years
Immunomonitoring (functional analysis looking at shifts in Th1/Th2/Th17)
functional analysis looking at shifts in Th1/Th2/Th17
Measured: 2 years
Immunomonitoring (plasmacytoid dendritic cells and myeloid derived suppressor cells and their IDO expression)
plasmacytoid dendritic cells and myeloid derived suppressor cells and their IDO expression,
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2015 (estimated)
- Study startMar 2015
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radiotherapie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Radiotherapie, University Hospital, Ghent
- Investigators
- Piet Ost, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02406183
- Sponsor's protocol ID
- EC 2015/0025
- Status last verified
- Jan 2017
- First submitted
- 17 Mar 2015
- Last updated
- 10 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Stereotactic Body Radiotherapy With Concurrent Fixed Dose Immune Checkpoint Inhibitors in Metastatic Melanoma: Dose Limiting Toxicity and Abscopal Effect
- ClinicalTrials.gov ID
- NCT02406183
- Acronym / sponsor ID
- EC 2015/0025
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- RadiotherapieUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 2 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The prognosis of advanced metastatic melanoma remains poor although a breakthrough has been achieved with the novel anti-CTLA-4 treatment (ipilimumab) for a subset of patients. Unfortunately, due to immune resistance, the majority of patients do not obtain long-lasting clinical benefit. Radiotherapy is able to interfere with immune resistance by inducing immunogenic cell death. Preclinical evidence indicates that combining radiotherapy with anti-CTLA-4 treatment increases response rates compared to single agent treatment. These data are supported by several spectacular clinical cases and one retrospective study. The investigators hypothesize that combining ipilimumab with radiotherapy will result in a higher response rate compared to ipilimumab or radiotherapy in monotherapy. Given the complexity of the interaction in anti-tumor immunity, the first goal of this project is to assess the safety of the combined treatment.
Detailed description
The safety profiles of ipilimumab and SBRT are well studied separately 22-24, but prospective data on the combination of ipilimumab and high-dose SBRT are lacking. Consequently, the first goal of the proposed prospective phase I trial is to assess the safety (dose limiting toxicity, DLT) of the combination of high-dose SBRT and ipilimumab in patients with advanced melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (SBRT, Ipilimumab) | Experimental | Radiation: Stereotactic body radiotherapy (SBRT), Drug: IpilimumabDrug: Ipilimumab Dosage: Ipilimumab will be administered intravenously at 3 mg/kg every 3 weeks for 4 cycles, Radiation: Stereotactic Body Radiotherapy Radiation therapy 24 Grays in 8 Grays fractions, Radiation therapy 30 Grays in 10 Grays fractions, Radiation therapy 36 Grays in 12 Grays fractions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed informed consent and willingness to comply to the treatment and follow-up
- Histological diagnosis of melanoma,
- at least 3 extracranial measurable metastatic lesions per RECIST 1.1,
- Karnofsky Performance score >60,
- Age ≥18,
Key exclusion criteria (10 listed)
- Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants.
- Prior malignancy: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- Prior radiotherapy preventing treatment with SBRT.
- Disorder precluding understanding of trial information.
- Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic body radiotherapy (SBRT)Also: SABRThe SBRT dose will be escalated in 3 steps as described above and will be given on d39, d41 and d43 | Radiation | Treatment (SBRT, Ipilimumab) |
| IpilimumabAlso: YervoyIpilimumab 3mg/kg will be given IV on d1, d22, d43 and d64 | Drug | Treatment (SBRT, Ipilimumab) |
Primary outcome
Maximal tolerated dose (MDT) that is associated with dose-limiting toxicity (DLT) in 25% of patients.
Time frame: 2 years
7 secondary outcomes
Preliminary anti-tumor activity following escalating doses of radiation combined to ipilimumab using the immune related response criteria irRC
Time frame: 2 years
Overall survival
Time frame: 2 years
Progression-free survival
Time frame: 2 years
Immunomonitoring (absolute lymphocyte count)
Time frame: 2 years
Immunomonitoring (frequencies of Foxp3+ Treg-cells)
Time frame: 2 years
Immunomonitoring (functional analysis looking at shifts in Th1/Th2/Th17)
Time frame: 2 years
Immunomonitoring (plasmacytoid dendritic cells and myeloid derived suppressor cells and their IDO expression)
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piet Ost, MD, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Stereotactic body radiotherapy (SBRT) and Ipilimumab in people with Melanoma and Effects of Immunotherapy, run by Radiotherapie at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal tolerated dose (MDT) that is associated with dose-limiting toxicity (DLT) in 25% of patients. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2017.