Metastatic MelanomaPhase 2NCT01689974
Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma
A Phase 2 study testing Ipilimumab and Radiation Therapy in people with Metastatic Melanoma, run by NYU Langone Health at 1 site in United States.
Trial summary
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub"… Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Ipilimumab and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to Mar 2015
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to sign a written informed consent document;
- Histologic diagnosis of locally unresectable, metastatic melanoma.
- Any BRAF status is permitted
- Any prior therapy is permitted except prior therapy with ipilimumab.
- Patients must have at least 2 distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter and may have additional non-measurable but established metastatic lesions (i.e. bone metastases).
- Patients must have adequate organ and marrow function as defined by initial laboratory tests:
Show all 18Show fewer
- WBC 2000/uL
- ANC 1000/uL
- Platelets 50 x 103/uL
- Hemoglobin 8 g/dL
- Creatinine 3.0 x ULN
- AST/ALT 2.5 x ULN for patients without liver metastasis
- Bilirubin 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL;
- Performance status ECOG 0-1 or Karnofsky > 50%;
- Men and women, ages > 18 year old of age;
- Life expectancy > 3 months
- Stable brain metastases for at least 4 weeks and not steroid dependent;
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study.
Who cannot join
- Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
- Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis;
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea;
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab);
- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;
- Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding;
- Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped;
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Clinical Cancer Center
New York, New York, 10016
About this study
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.[2]
Read the detailed description
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to generate important information for hypothesis-driven research about the mechanisms behind the clinical findings, to be tested in the laboratory.
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.[2]
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to generate important information for hypothesis-driven research about the mechanisms behind the clinical findings, to be tested in the laboratory.
The specific aims of the study are:
- To explore the induction of immunity-mediated tumor response outside the radiation field (abscopal effect) after radiation/Ipilimumab in metastatic melanoma, by estimating and comparing response rates in patients treated with Ipilimumab alone (Arm A) versus ipilimumab and radiation (Arm B).
- To compare the induction of a T-cell response in patients with metastatic melanoma treated with either ipilimumab alone or in combination with radiation.
All patients with metastatic melanoma with at least 2 measurable sites of disease are eligible. Extent of metastatic disease is recorded by CT scanning or MRI before therapy. Patients will then be randomized to Ipilimumab 3 mg/kg IV over 90 minutes alone versus Ipilimumab 3 mg/kg IV over 90 minutes plus radiotherapy to one of their measurable lesions, 6 Gy delivered daily x 5 days (Monday through Friday) (conformally or by IMRT/IGRT, to maximally spare normal tissue), for a total of 30 Gy. For patients assigned to the Ipilimumab/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4 from the first radiotherapy fraction. All patients will then have ipilimumab infusions repeated on Days 25, 46 and 67. Patients will be re-imaged (CT imaging or MRI) on Week 12 and evaluated for response (defined as an objective response of another metastatic site outside the radiation field).
The main immunological end-point will be the induction or boosting of treatment induced T cells (CD4+ and CD8+) and B cells for defined antigen approaches. In addition, the magnitude and duration of T- and B-cell responses will be examined. Treatment-induced responses will be calculated as the difference between the pre-treatment measurement and the measurement at the different time points at which blood will be collected (time of evaluation) in the same patient. The percentage of patients with the induction of treatment-induced T- and B-cell responses will be reported.
- Conditions
- Metastatic Melanoma
- Being tested
- Ipilimumab, Radiation Therapy
- Keywords
- Metastatic Melanoma, Radiation Therapy, Immunology, Abscopal
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Ipilimumab will be administered alone on day 4, 25, 46 and 67.
Radiation TherapyRadiation
Radiation is given over one week interval On the fourth day of radiation (day 4)Ipilimumab is administered and repeated on Days 25, 46 and 67.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Ipilimumab | Other | Ipilimumab administered alone Day 4, 25, 46, and 67 Receives: Drug: Ipilimumab |
| Arm B: Ipilimumab and Radiation | Other | Radiation Therapy and Ipilimumab. Radiation treatment is administered for 5 fractions (sessions) over 1 week. On Day 4 treatment with Ipilimumab begins and continues on Days 25, 46, and 67. Receives: Drug: Ipilimumab; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rates of Ipilimumab Alone and of Ipilimumab With Radiation Therapy and to Estimate the Difference Between Response Rates With Ipilimumab Alone and Ipilimumab With Radiation Therapy
Eligible patients have metastatic melanoma with at least 2 measurable sites of disease. All patients with metastatic melanoma are eligible to be randomly assigned to Ipilimumab 3mg/kg IV over 90 minutes versus Ipilimumab 3 mg/kg IV over 90 minutes and radiotherapy to one of their measurable lesions, 6 Gy X5 (conformally or by IMRT/IGRT, to maximally spare normal tissue). For patients assigned to the Ipi/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4 from the first radiotherapy fraction and repeated on Days 25, 46 and 67. Patients will be re-imaged on Week 12 and evaluated for response (defined as an objective response of another metastatic site outside the radiation field). This response will be evaluated assessing clinical and CT responses in the non-irradiated measurable metastatic sites.
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 posted21 Sep 2012 (estimated)
- Study startJan 2013
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: Study terminated because PI left institution. Planned Statistical analysis not available
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 Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Silvia C. Formenti, M.D., Principal investigator, NYULMC Department Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01689974
- Sponsor's protocol ID
- 12-02746
- Status last verified
- Jan 2018
- First submitted
- 18 Sep 2012
- Last updated
- 23 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01689974
- Acronym / sponsor ID
- 12-02746
- Conditions
- Metastatic Melanoma
- Keywords
- Metastatic Melanoma, Radiation Therapy, Immunology, Abscopal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated because PI left institution. Planned Statistical analysis not available
- Enrolment
- 10 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 21 Sep 2012 (estimated)
- Results
- Posted 23 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.[2]
Detailed description
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to generate important information for hypothesis-driven research about the mechanisms behind the clinical findings, to be tested in the laboratory.
An attractive area of research regards immune manipulations to recover some of the patient's immune response to his/her tumor, a strategy that has the advantages of being both natural and potentially long-lasting.[1] We propose to combine immunotherapy with radiotherapy directed to a metastatic site, to create a "hub" for in vivo immunization to the tumor, to enable "tumor rejection" at the other metastatic sites. This "in vivo immunization" is explored as a viable alternative to an individualized vaccine approach. Preclinical data generated by us and others support a "proof of principle" clinical trial that may open the field to an alternative use of radiotherapy in a novel partnership with cancer immunotherapy.[2]
In addition, we propose to perform immune-monitoring of the patients accrued to the trial to generate important information for hypothesis-driven research about the mechanisms behind the clinical findings, to be tested in the laboratory.
The specific aims of the study are:
- To explore the induction of immunity-mediated tumor response outside the radiation field (abscopal effect) after radiation/Ipilimumab in metastatic melanoma, by estimating and comparing response rates in patients treated with Ipilimumab alone (Arm A) versus ipilimumab and radiation (Arm B).
- To compare the induction of a T-cell response in patients with metastatic melanoma treated with either ipilimumab alone or in combination with radiation.
All patients with metastatic melanoma with at least 2 measurable sites of disease are eligible. Extent of metastatic disease is recorded by CT scanning or MRI before therapy. Patients will then be randomized to Ipilimumab 3 mg/kg IV over 90 minutes alone versus Ipilimumab 3 mg/kg IV over 90 minutes plus radiotherapy to one of their measurable lesions, 6 Gy delivered daily x 5 days (Monday through Friday) (conformally or by IMRT/IGRT, to maximally spare normal tissue), for a total of 30 Gy. For patients assigned to the Ipilimumab/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4 from the first radiotherapy fraction. All patients will then have ipilimumab infusions repeated on Days 25, 46 and 67. Patients will be re-imaged (CT imaging or MRI) on Week 12 and evaluated for response (defined as an objective response of another metastatic site outside the radiation field).
The main immunological end-point will be the induction or boosting of treatment induced T cells (CD4+ and CD8+) and B cells for defined antigen approaches. In addition, the magnitude and duration of T- and B-cell responses will be examined. Treatment-induced responses will be calculated as the difference between the pre-treatment measurement and the measurement at the different time points at which blood will be collected (time of evaluation) in the same patient. The percentage of patients with the induction of treatment-induced T- and B-cell responses will be reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Ipilimumab | Other | Drug: IpilimumabIpilimumab administered alone Day 4, 25, 46, and 67 |
| Arm B: Ipilimumab and Radiation | Other | Drug: Ipilimumab, Radiation: Radiation TherapyRadiation Therapy and Ipilimumab. Radiation treatment is administered for 5 fractions (sessions) over 1 week. On Day 4 treatment with Ipilimumab begins and continues on Days 25, 46, and 67. |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Ability to understand and the willingness to sign a written informed consent document;
- Histologic diagnosis of locally unresectable, metastatic melanoma.
- Any BRAF status is permitted
- Any prior therapy is permitted except prior therapy with ipilimumab.
- Patients must have at least 2 distinct measurable metastatic sites, with one of at least 1 cm or larger in its largest diameter and may have additional non-measurable but established metastatic lesions (i.e. bone metastases).
Key exclusion criteria (8 listed)
- Patients having no lesions outside the field of radiation thus nullifying the ability to measure an abscopal effect;
- Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis;
- Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea;
- Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab);
- Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids;
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: YervoyIpilimumab will be administered alone on day 4, 25, 46 and 67. | Drug | Arm A: Ipilimumab, Arm B: Ipilimumab and Radiation |
| Radiation TherapyRadiation is given over one week interval On the fourth day of radiation (day 4)Ipilimumab is administered and repeated on Days 25, 46 and 67. | Radiation | Arm B: Ipilimumab and Radiation |
Primary outcome
Response Rates of Ipilimumab Alone and of Ipilimumab With Radiation Therapy and to Estimate the Difference Between Response Rates With Ipilimumab Alone and Ipilimumab With Radiation Therapy
Time frame: 2 years
Eligible patients have metastatic melanoma with at least 2 measurable sites of disease. All patients with metastatic melanoma are eligible to be randomly assigned to Ipilimumab 3mg/kg IV over 90 minutes versus Ipilimumab 3 mg/kg IV over 90 minutes and radiotherapy to one of their measurable lesions, 6 Gy X5 (conformally or by IMRT/IGRT, to maximally spare normal tissue). For patients assigned to the Ipi/RT arm, Ipilimumab treatment starts after radiotherapy, with a dose given on day 4 from the first radiotherapy fraction and repeated on Days 25, 46 and 67. Patients will be re-imaged on Week 12 and evaluated for response (defined as an objective response of another metastatic site outside the radiation field). This response will be evaluated assessing clinical and CT responses in the non-irradiated measurable metastatic sites.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Silvia C. Formenti, M.D. principal investigator
NYULMC Department Radiation Oncology
1 site 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 and Radiation Therapy in people with Metastatic Melanoma, run by NYU Langone Health at 1 site in United States.
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 18 inclusion and 8 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: stopped early, as of the sponsor's last update on 23 Feb 2018. 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 United States. 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 23 Feb 2018). 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?
Response Rates of Ipilimumab Alone and of Ipilimumab With Radiation Therapy and to Estimate the Difference Between Response Rates With Ipilimumab Alone and Ipilimumab With Radiation Therapy (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 23 Feb 2018.