Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01689974
Recruitment Status : Terminated (Study terminated because PI left institution. Planned Statistical analysis not available)
First Posted : September 21, 2012
Results First Posted : February 23, 2018
Last Update Posted : February 23, 2018
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Brief 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" 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]

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: Ipilimumab Radiation: Radiation Therapy Phase 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:

  1. 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).
  2. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Ipilimumab Versus Ipilimumab and Radiotherapy in Metastatic Melanoma
Study Start Date : January 2013
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Ipilimumab

Arm Intervention/treatment
Arm A: Ipilimumab
Ipilimumab administered alone Day 4, 25, 46, and 67
Drug: Ipilimumab
Ipilimumab will be administered alone on day 4, 25, 46 and 67.
Other Name: Yervoy

Arm B: Ipilimumab and Radiation
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.
Drug: Ipilimumab
Ipilimumab will be administered alone on day 4, 25, 46 and 67.
Other Name: Yervoy

Radiation: Radiation Therapy
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.




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01689974


Locations
Layout table for location information
United States, New York
NYU Clinical Cancer Center
New York, New York, United States, 10016
Sponsors and Collaborators
NYU Langone Health
Investigators
Layout table for investigator information
Principal Investigator: Silvia C. Formenti, M.D. NYULMC Department Radiation Oncology
Layout table for additonal information
Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT01689974    
Other Study ID Numbers: 12-02746
First Posted: September 21, 2012    Key Record Dates
Results First Posted: February 23, 2018
Last Update Posted: February 23, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by NYU Langone Health:
Metastatic Melanoma
Radiation Therapy
Immunology
Abscopal
Additional relevant MeSH terms:
Layout table for MeSH terms
Ipilimumab
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents