AzTrials
AzTrials

Recurrent MelanomaPhase 1NCT01703507

Phase I Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma

A Phase 1 study testing Ipilimumab, Whole-Brain Radiation Therapy (WBRT) and Stereotactic Radiosurgery (SRS) in people with Recurrent Melanoma and Stage IV Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of ipilimumab when given together with whole brain radiation therapy or stereotactic radiosurgery in treating patients with melanoma with brain metastases. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ipilimumab, Whole-Brain Radiation Therapy (WBRT) and Stereotactic Radiosurgery (SRS)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
2 sitesUnited States
Study dates
9 Nov 2012to 11 Apr 2018
Phase
Phase 1
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

  • Patient age is >= 18 years
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1.
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Patients must meet the following laboratory criteria:
  • WBC >= 2000/uL
  • ANC >= 1000/uL
Show all 37Show fewer
  • Platelets >= 75 x 10^3/uL
  • Hemoglobin >= 9 g/dL (>= 80 g/L; may be transfused)
  • AST/ALT <= 2.5 x ULN for patients without liver metastasis
  • AST/ALT <= 5 times for liver metastases
  • Bilirubin <= 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Serum creatinine <= 2.0 x ULN or 24-hour creatinine clearance >= 50 ml/min
  • Total serum calcium (corrected for serum albumin) or ionized calcium >= lower limit of normal (LLN)
  • Serum potassium >= LLN
  • Serum sodium >= LLN
  • Serum albumin >= LLN or 3g/dl
  • Patients with any elevated Alkaline Phosphatase due to bone metastases can be enrolled
  • No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  • Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
  • Amenorrhea >= 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL.
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the start of ipilimumab.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study (and for up to 26 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized.
  • A pathological diagnosis of melanoma is required, from either the primary or a metastasis. This also includes uveal melanoma.
  • A radiological diagnosis (CT or MRI) of one or more brain metastases is required.
  • Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade <= 1.
  • Specific eligibility criteria for the two arms
  • Arm A WBRT and Ipilimumab:
  • Patients have 5 or more brain metastases, or patients have any brain metastases exceeding the limit for SRS (maximum diameter is > 4 cm).
  • OR Patient has only one brain metastasis and completely resected, the resection cavity is > 4 cm in diameter.
  • Arm B SRS and Ipilimumab:
  • Patients have 4 or fewer brain metastases. All the brain metastases are <= 4 cm in diameter.
  • Patients have only one brain metastasis and completely resected, the resection cavity is <= 4 cm in diameter.
  • OR If a patient is found to have progression of brain metastases that exceed 4 cm in diameter based on the MRI scan on the time of SRS procedure, the patient should be re-assigned to WBRT arm or withdrawn from the study. The study PI should be notified.
  • OR If a patient is found to have progression of brain metastases that exceed 4 lesions based on the MRI scan on the time of the SRS procedure, the patient can either be treated with SRS to all the lesions (up to 10 lesions), re-assigned to WBRT arm, or withdrawn from the study per the treating physician. The study PI should be notified.

Who cannot join

  • Patient with leptomeningeal carcinomatosis.
  • Autoimmune disease: 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).
  • Major surgery or radiation therapy within 2 weeks of starting the study treatment.
  • If patients are receiving chemotherapy or other investigational drugs, they must be discontinued 4 weeks prior to enrollment.
  • NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment.
  • Any of the following within the 6 months prior to study drug administration:
Show all 22Show fewer
  • myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism. Patients with known cardiac disease will be required to have an ECHO or MUGA scan at baseline and at the completion of study.
  • Ongoing cardiac dysrhythmias of NCI CTCAE grade >= 2.
  • Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy).
  • Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection.
  • Pregnancy or breastfeeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens, cytotoxic chemotherapy, immunosuppressive agents, vermurafenib, or other investigational therapies.
  • All efforts need to be taken to avoid/minimize the use of cortical steroid during radiation period (1 week prior to start radiation, during radiation, and 1 week after finishing radiation). Any steroid used considered necessary by the treating physician should be closely documented, including medication, route of administration, dose, and duration.
  • Active infection with hepatitis B, or hepatitis C.
  • Patients who had prior brain radiation treatment.
  • Patients are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated basal or squamous cell carcinoma of skin, superficial bladder cancer or carcinoma in situ of cervix, AJCC (version 7.0) stage 0 or I breast cancer, AJCC (version 7.0) stage I, or II prostate cancer.
  • Patients are excluded if they have a history of autoimmune disease, as follows: 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]). Patients with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis) are excluded. Patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy.
  • Patients who are allergic to Ipilimumab.
  • Patients who received ipilimumab before.
  • Patients who are allergic to MRI contrast agent or have contraindication for MRI.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Ohio State University

    Columbus, Ohio, 43210

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Phase I Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases

This phase I trial studies the side effects and best dose of ipilimumab when given together with whole brain radiation therapy or stereotactic radiosurgery in treating patients with melanoma with brain metastases. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find Tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy, such uses high-energy x-rays and other types of radiation to kill tumor cells. Giving radiation therapy in different ways may kill more tumor cells. Giving ipilimumab together with whole-brain radiation therapy or stereotactic radiosurgery may kill more tumor cells.

Read the detailed description

Melanoma patients with brain metastases have a very poor outcome. Most patients with brain metastases will die from CNS related death. Radiation therapy is an effective treatment for patients with brain metastases for symptom palliation and survival benefit. Patients with multiple metastases are typically treated with whole brain radiation treatment (WBRT). For patients with a few metastases, stereotactic radiosurgery (SRS) alone can be used as an alternative. CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) antibody, Ipilimumab has shown efficacy in metastatic melanoma and unresectable melanoma. Treatment with high doses of radiation therapy would result in tumor cell death, releasing tumor debris and liberating potential tumor antigens. We hypothesize that combining radiation therapy with Ipilimumab will facilitate immune recognition of these novel tumor-specific antigens, yielding a synergistic effect. Further, the hypothesis of this study is that this combination could focus the immune system on tumor antigens and minimize the aberrant immune activation in normal tissues, consequently reducing the incidence of irAE's (immune related adverse effect). Combination of radiation treatment with Ipilimumab will likely result in better local control, decrease the risk of developing new brain metastases, and improved overall survival. However, the safety profile and toxicities of combining Ipilimumab with brain radiation treatment are unknown. The current phase I study will assess the safety profile of combining different doses of Ipilimumab with standard dose radiation treatment either with WBRT or SRS. The MTD (maximum tolerated dose) will be determined, as well as a recommended phase II trial dose of Ipilimumab.

Being tested
Ipilimumab, Whole-Brain Radiation Therapy (WBRT), Stereotactic Radiosurgery (SRS)
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IpilimumabDrug

    Also called MDX-010, MDX-101, Yervoy

    Given IV

  • Whole-Brain Radiation Therapy (WBRT)Radiation

    Also called WBRT, Whole-brain radiotherapy

    Undergo WBRT

  • Stereotactic Radiosurgery (SRS)Radiation

    Undergo SRS

Study groups in NCT01703507
Study groupRoleWhat they receive
Arm A (Ipilimumab and Whole Brain Radiation Therapy)ExperimentalPatients receive ipilimumab IV over 90 minutes once in weeks 1, 4, 7, and 10. Patients also undergo WBRT 5 days a week in weeks 1-2.
Receives: Drug: Ipilimumab; Radiation: Whole-Brain Radiation Therapy (WBRT)
Arm B (Ipilimumab and Stereotactic Radiosurgery)ExperimentalPatients receive ipilimumab IV over 90 minutes as in Arm A. Patients also undergo SRS on day 1 in week 1.
Receives: Drug: Ipilimumab; Radiation: Stereotactic Radiosurgery (SRS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Ipilimumab

    (MTD) when combined with WBRT or SRS, defined as the last dose studied or the previous dose, based on clinical judgment of the degree of toxicity seen at the last dose

    Measured: 30 days following the completion of radiation therapy

Secondary outcomes (5)

  1. Rate of Developing New Brain Metastases in Each Arm

    Measured: Up to 5 years

  2. Number of Subjects With Response of Extracranial Disease

    Extracranial disease is assessed through repeated computed tomography of the chest, abdomen, and pelvis. The purpose of this scan is to determine if there is any evidence of disease outside of the brain.

    Measured: Up to 5 years

  3. Overall Survival (OS) Rate

    Measured: Up to 5 years

  4. Number of Patients With Progression Free Survival (PFS) Rate

    PFS rate based on Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related response criteria (irRC) criteria based on the brain MRI and systematic assessment by the treating physician

    Measured: Up to 5 years

  5. Number of Participants With Adverse Events and Serious Adverse Events

    Measured: 4 weeks following the last dose of ipilimumab

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Oct 2012 (estimated)
  2. Study start9 Nov 2012
  3. Primary completion20 May 2015
  4. Study completion11 Apr 2018

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01703507
Sponsor's protocol ID
12P.314
Other IDs
2012-43, JT 2988
Status last verified
May 2025
First submitted
5 Oct 2012
Last updated
16 May 2025
Data monitoring committee
Yes

Publications

  • Bafaloukos D, Gogas H. The treatment of brain metastases in melanoma patients. Cancer Treat Rev. 2004 Oct;30(6):515-20. doi: 10.1016/j.ctrv.2004.05.001.

    PubMed 15325032

  • Barth A, Wanek LA, Morton DL. Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg. 1995 Sep;181(3):193-201.

    PubMed 7670677

  • Sampson JH, Carter JH Jr, Friedman AH, Seigler HF. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg. 1998 Jan;88(1):11-20. doi: 10.3171/jns.1998.88.1.0011.

    PubMed 9420067

  • Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, Markesbery WR, Foon KA, Young B. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998 Nov 4;280(17):1485-9. doi: 10.1001/jama.280.17.1485.

    PubMed 9809728

  • Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990 Feb 22;322(8):494-500. doi: 10.1056/NEJM199002223220802.

    PubMed 2405271

  • Andrews DW. Current neurosurgical management of brain metastases. Semin Oncol. 2008 Apr;35(2):100-7. doi: 10.1053/j.seminoncol.2007.12.003.

    PubMed 18396195

  • Thomas SS, Dunbar EM. Modern multidisciplinary management of brain metastases. Curr Oncol Rep. 2010 Jan;12(1):34-40. doi: 10.1007/s11912-009-0073-8.

    PubMed 20425606

  • CHU FC, HILARIS BB. Value of radiation theray in the management of intracranial metastases. Cancer. 1961 May-Jun;14:577-81. doi: 10.1002/1097-0142(199005/06)14:33.0.co;2-f. No abstract available.

    PubMed 13693470

  • Expert Panel on Radiation Oncology-Brain Metastases; Videtic GM, Gaspar LE, Aref AM, Germano IM, Goldsmith BJ, Imperato JP, Marcus KJ, McDermott MW, McDonald MW, Patchell RA, Robins HI, Rogers CL, Suh JH, Wolfson AH, Wippold FJ 2nd. American College of Radiology appropriateness criteria on multiple brain metastases. Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):961-5. doi: 10.1016/j.ijrobp.2009.07.1720. No abstract available.

    PubMed 19857783

  • DiLuna ML, King JT Jr, Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer. 2007 Jan 1;109(1):135-45. doi: 10.1002/cncr.22367.

    PubMed 17133440

  • Manon R, O'Neill A, Knisely J, Werner-Wasik M, Lazarus HM, Wagner H, Gilbert M, Mehta M; Eastern Cooperative Oncology Group. Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J Clin Oncol. 2005 Dec 1;23(34):8870-6. doi: 10.1200/JCO.2005.01.8747.

    PubMed 16314647

  • Mathieu D, Kondziolka D, Cooper PB, Flickinger JC, Niranjan A, Agarwala S, Kirkwood J, Lunsford LD. Gamma knife radiosurgery for malignant melanoma brain metastases. Clin Neurosurg. 2007;54:241-7. No abstract available.

    PubMed 18504926

  • Clarke JW, Register S, McGregor JM, Grecula JC, Mayr NA, Wang JZ, Li K, Gupta N, Kendra KL, Olencki TE, Cavaliere R, Sarkar A, Lo SS. Stereotactic radiosurgery with or without whole brain radiotherapy for patients with a single radioresistant brain metastasis. Am J Clin Oncol. 2010 Feb;33(1):70-4. doi: 10.1097/COC.0b013e31819ccc8c.

    PubMed 19652578

  • Order SE, Hellman S, Von Essen CF, Kligerman MM. Improvement in quality of survival following whole-brain irradiation for brain metastasis. Radiology. 1968 Jul;91(1):149-53. doi: 10.1148/91.1.149. No abstract available.

    PubMed 4172540

  • Khuntia D, Brown P, Li J, Mehta MP. Whole-brain radiotherapy in the management of brain metastasis. J Clin Oncol. 2006 Mar 10;24(8):1295-304. doi: 10.1200/JCO.2005.04.6185.

    PubMed 16525185

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ipilimumab, Whole-Brain Radiation Therapy (WBRT) and Stereotactic Radiosurgery (SRS) in people with Recurrent Melanoma and Stage IV Melanoma, run by Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University at 2 sites 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 37 inclusion and 22 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 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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?

Yes. Results are posted in the registry (first posted 19 Aug 2019). 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?

Maximum Tolerated Dose (MTD) of Ipilimumab (time frame: 30 days following the completion of radiation therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01703507, which also lists 60 linked publications.

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 16 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in