MelanomaPhase 2GRAY-BNCT02115139
GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases
A Phase 2 study testing Ipilimumab in people with Melanoma and Brain Metastases, run by Grupo Español Multidisciplinar de Melanoma at 12 sites in Spain.
Trial summary
Ipilimumab adds a clinical benefit to radiation therapy in patients with melanoma metastatic to the brain. Melanoma is the third most common cancer causing brain metastases, after cancers of the lung and breast, which appears to reflect the relative propensity of melanoma to metastasize to the central nervous system… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Brain Metastases
- What is being tested?
- Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 12 sitesSpain
- Study dates
- 4 Apr 2014to 31 Jul 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Willing and able to give written informed consent.
- Histologic diagnosis of melanoma.
- First episode of radiological evidence of brain metastases
- Be over the age of 18 years old
- Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) class 2
- Karnofsky performance status (PS) more than 70%
Show all 17Show fewer
- Barthel Index of Activities of Daily Living more than 10
- Measurable disease (mWHO criteria).
- Adequate organ function as determine by the following criteria:
- White blood count (WBC) more or equal to 2000/ microliter (uL)
- Absolute neutrophil count (ANC) more than 1.5 x 109/L.
- Platelet count more than 75 x 109/L.
- Hemoglobin more than 9 g/dL. If the patient received a red blood count (RBC) transfusion, the required value of hemoglobin should be met at least 1 week after the most recent transfusion.
- Serum creatinine less or equal to 2.0 x upper limit of normal (ULN).
- Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) less or equal to 2.5 x ULN for patients without liver metastasis, or less or equal to 5 times for liver metastases.
- Total bilirubin less or equal 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped
Who cannot join
- Patients with melanoma and brain metastases with any of the following disease-specific characteristics:
- Documented evidence of prior progression of melanoma to an ipilimumab-containing regimen (i.e. received at least 2 doses of ipilimumab for either advanced disease or in the adjuvant setting and the disease progressed/relapsed (according to mWHO criteria) within 24 weeks since the first dose of ipilimumab)
- Prior radiation therapy to the brain
- Other prior antineoplastic therapies for brain metastases.
- Patients with cerebral metastases as the only location of the disease, for which local therapy (neurosurgery, radiosurgery) could achieve a disease-free status
- Patients with a rapid clinical deterioration, or with risk of herniation, or who require unstable ascending dosing of supportive medication in the last week -including anti-convulsivants, steroids and analgesics-, or who require dexamethasone more than 16 mg/d (or other glucocorticoid at an equipotent dose), or with a high lactate dehydrogenase (LDH) more than 2 x ULN.
Show all 17Show fewer
- Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or incidental prostate cancer.
- Uncontrolled diabetes mellitus (HbA1c more than 9 %)
- Autoimmune disease other than vitiligo or past thyroiditis under substitutive hormone therapy: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- Other chronic intestinal diseases associated with diarrhea.
- Active infection or other serious illness or medical condition.
- Known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
- Concomitant therapy with any of the following: interleukin-2 (IL-2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used for the management of non-cancer related illnesses), either concomitantly or during the last 30 days prior to the beginning of the treatment.
- Any experimental therapy administered in the past 30 days prior to the beginning of the treatment.
- Any non-oncology vaccine therapy used for the prevention of infectious diseases (for up to 4 weeks prior to or after any dose of blinded study drug) (see definitions in protocol text)
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
- Any other general, medical or psychological conditions which in the opinion of the investigator will make the administration of ipilimumab hazardous, or that would preclude appropriate informed consent or compliance with the protocol, or obscure the interpretation of eventual adverse events (AEs).
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Spain12 sites
ICO Badalona
Badalona
H. Clinic de Barcelona
Barcelona
Hospital Vall d'Hebron
Barcelona
H. Insular de Canarias
Las Palmas de Gran Canaria
H. U. Gregorio Marañón
Madrid
Hospital Universitario 12 de Octubre
Madrid
Clínica Universidad de Navarra
Pamplona
H. Clínico de Santiago
Santiago de Compostela
H.U. Virgen Macarena
Seville
H. Virgen de la Salud
Toledo
H. General de Valencia
Valencia
Instituto Valenciano de Oncología
Valencia
About this study
Official title: A Multicenter, Single Arm, Phase 2 Clinical Study on the Combination of Radiation Therapy and Ipilimumab, for the Treatment of Patients With Melanoma and Brain Metastases
Ipilimumab adds a clinical benefit to radiation therapy in patients with melanoma metastatic to the brain.
Melanoma is the third most common cancer causing brain metastases, after cancers of the lung and breast, which appears to reflect the relative propensity of melanoma to metastasize to the central nervous system (CNS). Brain metastases are responsible for 20 to 54 percent of deaths in patients with melanoma, and among those with documented brain metastases, these lesions contribute to death in up to 95 percent of cases, with an estimated median overall survival ranging between 1.8 and 10.5 months, depending upon other prognostic factors.
Read more
Ipilimumab is an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) monoclonal antibody that has demonstrated a clinically relevant and statistically significant improvement in overall survival, either alone (second line) or in combination with dacarbazine (DTIC) in 1st line.
Ipilimumab has shown activity against brain metastases.
According to the European Medicines Agency (EMA) approved label for Yervoy®, the use of glucocorticoids at baseline (commonly prescribed when brain metastases are diagnosed) should be avoided before the administration of ipilimumab. Data show that the use of even high doses of glucocorticoids for the management of immune-related adverse events do not decrease the efficacy of Yervoy®. There is no documented experience on the efficacy of Yervoy® when given concomitantly with radiation therapy and glucocorticoids.
In experimental models, radiation therapy is synergistic to anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) strategies (abscopal effect).
There are no published results from clinical trials on the interaction between radiation therapy and ipilimumab.
- Conditions
- Melanoma, Brain Metastases
- Being tested
- Ipilimumab
- Keywords
- melanoma, brain, metastases, Patients with melanoma and brain metastases
- Medical subject headings
- Melanoma, Brain Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Experimental
Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| Ipilimumab | Experimental | Ipilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 Receives: Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year Survival Rate
During treatment period, there will be assessments every cycle. After end of treatment every 3 month.
Measured: From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months. Up to 1 year
Secondary outcomes (7)
Progression-Free Survival (PFS)
Median time from treatment initiation to progression of disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Intracranial PFS
median, 6-month PFS rate
Measured: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Extracranial PFS
median, 6-month PFS rate
Measured: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Overall Survival
median value for OS estimated by kaplan meier method
Measured: From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months.
Response Rate
Measured according to Who response criteria and Immune-related response criteria.
Response for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Adverse Event Rates
Number of patients with at least one treatment-related toxicity, classified by grade.
Measured: From date of inclusion until the date of first documented date of death from any cause or end of study, assessed every 3 weeks during for the first 6 months, then every 3 months.
Rate of Dose Delays/Reductions and Treatment Exposure.
Treatment feasibility. Number of patients with treatment delays and reductions, categorized as function of the number of events (reductions/delays)
Measured: Expected average of 3 weeks during for the first 6 months, then every 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study start4 Apr 2014
- Primary completion31 Dec 2016
- Study completion31 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Español Multidisciplinar de Melanoma
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- José A López-Martín, MD, Study chair, Hospital Universitario 12 de Octubre - GEM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115139
- Sponsor's protocol ID
- GEM 1202
- Other IDs
- 2013-001132-22
- Acronym
- GRAY-B
- Status last verified
- Oct 2022
- First submitted
- 10 Apr 2014
- Last updated
- 8 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single Arm, Phase 2 Clinical Study on the Combination of Radiation Therapy and Ipilimumab, for the Treatment of Patients With Melanoma and Brain Metastases
- ClinicalTrials.gov ID
- NCT02115139
- Acronym / sponsor ID
- GRAY-B / GEM 1202
- Conditions
- Melanoma, Brain Metastases
- Keywords
- melanoma, brain, metastases, Patients with melanoma and brain metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Grupo Español Multidisciplinar de MelanomaUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 4 Apr 2014 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 15 Apr 2014 (estimated)
- Results
- Posted 1 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ipilimumab adds a clinical benefit to radiation therapy in patients with melanoma metastatic to the brain.
Melanoma is the third most common cancer causing brain metastases, after cancers of the lung and breast, which appears to reflect the relative propensity of melanoma to metastasize to the central nervous system (CNS). Brain metastases are responsible for 20 to 54 percent of deaths in patients with melanoma, and among those with documented brain metastases, these lesions contribute to death in up to 95 percent of cases, with an estimated median overall survival ranging between 1.8 and 10.5 months, depending upon other prognostic factors.
Ipilimumab is an anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) monoclonal antibody that has demonstrated a clinically relevant and statistically significant improvement in overall survival, either alone (second line) or in combination with dacarbazine (DTIC) in 1st line.
Ipilimumab has shown activity against brain metastases.
According to the European Medicines Agency (EMA) approved label for Yervoy®, the use of glucocorticoids at baseline (commonly prescribed when brain metastases are diagnosed) should be avoided before the administration of ipilimumab. Data show that the use of even high doses of glucocorticoids for the management of immune-related adverse events do not decrease the efficacy of Yervoy®. There is no documented experience on the efficacy of Yervoy® when given concomitantly with radiation therapy and glucocorticoids.
In experimental models, radiation therapy is synergistic to anti-Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) strategies (abscopal effect).
There are no published results from clinical trials on the interaction between radiation therapy and ipilimumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ipilimumab | Experimental | Drug: IpilimumabIpilimumab 3mg/Kg iv q 3 weeks for 4 cycles Whole-brain radiotherapy (WBRT) 30 Gy in 10 fractions (or radiobiological equivalent schedule, after Sponsor approval), starting between Cycle 1 Day 2 and Cycle 2 Day 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Willing and able to give written informed consent.
- Histologic diagnosis of melanoma.
- First episode of radiological evidence of brain metastases
- Be over the age of 18 years old
- Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) class 2
Key exclusion criteria (17 listed)
- Patients with melanoma and brain metastases with any of the following disease-specific characteristics:
- Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, or incidental prostate cancer.
- Uncontrolled diabetes mellitus (HbA1c more than 9 %)
- Autoimmune disease other than vitiligo or past thyroiditis under substitutive hormone therapy: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
- Other chronic intestinal diseases associated with diarrhea.
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 |
|---|---|---|
| IpilimumabAlso: ExperimentalIpilimumab 3mg/Kg iv q 3 weeks for 4 cycles | Drug | Ipilimumab |
Primary outcome
1-year Survival Rate
Time frame: From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months. Up to 1 year
During treatment period, there will be assessments every cycle. After end of treatment every 3 month.
7 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Intracranial PFS
Time frame: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Extracranial PFS
Time frame: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Overall Survival
Time frame: From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months.
Response Rate
Time frame: Within 4 weeks before start treatment, week 12, 17+/-1 and every 9 + / -1 weeks until progression up to 12 months after last patient treatment initiation.
Adverse Event Rates
Time frame: From date of inclusion until the date of first documented date of death from any cause or end of study, assessed every 3 weeks during for the first 6 months, then every 3 months.
Rate of Dose Delays/Reductions and Treatment Exposure.
Time frame: Expected average of 3 weeks during for the first 6 months, then every 3 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
José A López-Martín, MD study chair
Hospital Universitario 12 de Octubre - GEM
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab in people with Melanoma and Brain Metastases, run by Grupo Español Multidisciplinar de Melanoma at 12 sites in Spain.
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 17 inclusion and 17 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 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
1-year Survival Rate (time frame: From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months. Up to 1 year). 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 8 Nov 2022.