SRS (Stereotactic Radiosurgery) Plus Ipilimumab

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01950195
First received: June 21, 2013
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

This research is being done to look at the safety of using stereotactic radiosurgery (SRS) and Ipilimumab together to treat melanoma that has spread to the brain or spine. Both Ipilimumab and SRS are used alone for the treatment of melanoma that has spread. Standard of care uses both of these treatments but not together. By using them together, we expect better treatment of melanoma, but there might be an increase in side effects.

"Ipilimumab" is approved by the Food and Drug Administration (FDA) for the treatment of melanoma that has spread throughout the body. It works by activating your immune system to fight off cancer.

"Stereotactic radiosurgery" (SRS) is approved by the Food and Drug Administration (FDA) for the treatment of melanoma in the brain or spine. It uses radiation to treat tumors without needing to cut or use stitches.

The use of combining SRS and Ipilimumab in this research study is investigational. The word "investigational" means that this combination is not approved for marketing by the Food and Drug Administration but is allowed for use in this research study.


Condition Intervention Phase
Newly Diagnosed Melanoma Metastases in the Brain and Spine
Procedure: Stereotactic Radiosurgery (SRS)
Biological: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Stereotactic Radiosurgery Combined With Ipilimumab in Patients With Newly Diagnosed Melanoma Metastases in the Brain and Spine

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of adverse events and severity of the adverse events. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To assess the safety profile of stereotactic radiosurgery with ipilimumab in combination to treat patients with newly diagnosed melanoma brain or spinal metastases.


Secondary Outcome Measures:
  • To estimate local control rate in brain and spine [ Time Frame: 1 years ] [ Designated as safety issue: Yes ]
    To estimate systematic control rate; To estimate progression-free survival


Other Outcome Measures:
  • Correlative Objective [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To explore peripheral blood immune response during and after treatment


Estimated Enrollment: 30
Study Start Date: September 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Brain

A cohort of six (6) patients will be treated at Dosing Schedule 1. If the observed dose limiting toxicity (DLT) rate is less ≤33%, the dose cohort will be expended to a total of 15 patients. Brain and spine metastases will be evaluated as two separate cohorts.

If the first schedule produces DLTs in >33% of patients, the Second Dosing schedule will be implemented. If the second dosing schedule produces DLTs in >33% of patients, the Third Dosing schedule will be implemented.

After 6 patients were enrolled in a cohort, their safety and toxicity will be continuously monitored till 12 weeks (3 months) after the initial dose of Ipilimumab is given for evaluating dose-limiting toxicities.

Procedure: Stereotactic Radiosurgery (SRS) Biological: Ipilimumab
Experimental: Spine

A cohort of six (6) patients will be treated at Dosing Schedule 1. If the observed dose limiting toxicity (DLT) rate is less ≤33%, the dose cohort will be expended to a total of 15 patients. Brain and spine metastases will be evaluated as two separate cohorts.

If the first schedule produces DLTs in >33% of patients, the Second Dosing schedule will be implemented. If the second dosing schedule produces DLTs in >33% of patients, the Third Dosing schedule will be implemented.

After 6 patients were enrolled in a cohort, their safety and toxicity will be continuously monitored till 12 weeks (3 months) after the initial dose of Ipilimumab is given for evaluating dose-limiting toxicities.

Procedure: Stereotactic Radiosurgery (SRS) Biological: Ipilimumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically confirmed diagnosis of melanoma. The pathologic confirmation may be from another metastatic site or from metastatic brain or spine lesions.
  2. Patients must have Stage IV melanoma, with newly identified brain or spine metastases.
  3. Patients must have measurable lesion in the brain or spine that is > 3 mm seen on magnetic resonance imaging (MRI) with contrast.

    NOTE: Contrasted pre-treatment MRI scan must be obtained ≤ 21 days prior to stereotactic radiosurgery treatment.

  4. Karnofsky Performance Scale >70%
  5. Patients must have normal organ and marrow function as defined below:

    leukocytes >3,000/mcL absolute neutrophil count >1,500/mcL platelets >100,000/mcL total bilirubin ≤2X institutional upper limit of normal AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal creatinine within normal institutional limits OR According to Johns Hopkins MRI policy

  6. Women of child bearing potential (WOCBP) using a reliable form of contraception during the study treatment period and for up to 12 weeks following the last dose of study drug [21].
  7. Men must agree to the use of male contraception during the study treatment period and for at least 12 weeks after the last dose of study drug.
  8. Ability to understand and the willingness to sign written informed consent document(s).

Exclusion Criteria:

  1. Prior whole brain radiation or conventional radiation to the spine at the site of new lesion.
  2. Prior chemotherapy within 28 days of starting treatment.
  3. Prior therapy with investigational drugs within 28 days or at least 5 half-lives (whichever is longer) before study administration.
  4. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody.
  5. Neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  6. Known allergy to compounds of similar chemical or biologic composition to ipilimumab.
  7. Pregnant or breastfeeding women.
  8. Known history of Human Immunodeficiency Virus.
  9. Active infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA) [11].
  10. Active autoimmune disease, history of autoimmune disease or history of syndrome that required systemic steroids or immunosuppressive medications. Exceptions include those with vitiligo or resolved childhood asthma/atopy. Subjects with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study [11].
  11. Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up to 4 weeks (28 days) before receiving ipilimumab.
  12. Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
  13. Patients with both brain and spine metastases will be excluded from the trial.
  14. Patients who are allergic to MRI contrast agent or have contraindication for MRI.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01950195

Contacts
Contact: Susan Zhen, BSN 410-502-4081 szhen1@jhmi.edu
Contact: Michael Lim, MD 410-614-1627

Locations
United States, Maryland
The Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Susan Zhen, BSN    410-502-4081      
Contact: Hongyan Cai, MS    410-502-7752      
Principal Investigator: Michael Lim, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Michael Lim, MD Johns Hopkins Department of Neurosurgery
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01950195     History of Changes
Other Study ID Numbers: J1382
Study First Received: June 21, 2013
Last Updated: March 18, 2014
Health Authority: United States: Johns Hopkins University Institutional Review Board
United States: Johns Hopkins University, SKCCC CRO

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Melanoma
Metastases
Brain
Spine
SRS(Stereotactic Radiosurgery))
Ipilimumab

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on September 18, 2014