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

NCT01703507 | Completed Phase 1 Results DMC

• 3 other identifiers: 12P.3142012-43JT 2988
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Recurrent Melanoma; Stage IV Melanoma; Tumors Metastatic to Brain

Outcome Measures

Primary Outcomes (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

  30 days following the completion of radiation therapy

Secondary Outcomes (5)

• Rate of Developing New Brain Metastases in Each Arm

  Up to 5 years

• Number of Subjects With Response of Extracranial Disease

  Up to 5 years

• Overall Survival (OS) Rate

  Up to 5 years

• Number of Patients With Progression Free Survival (PFS) Rate

  Up to 5 years

• Number of Participants With Adverse Events and Serious Adverse Events

  4 weeks following the last dose of ipilimumab

Study Arms (2)

Arm A (Ipilimumab and Whole Brain Radiation Therapy)

EXPERIMENTAL

Patients 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.

Drug: Ipilimumab; Radiation: Whole-Brain Radiation Therapy (WBRT)

Arm B (Ipilimumab and Stereotactic Radiosurgery)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes as in Arm A. Patients also undergo SRS on day 1 in week 1.

Drug: Ipilimumab; Radiation: Stereotactic Radiosurgery (SRS)

Interventions

Ipilimumab DRUG

Given IV

Also known as: MDX-010, MDX-101, Yervoy

Arm A (Ipilimumab and Whole Brain Radiation Therapy); Arm B (Ipilimumab and Stereotactic Radiosurgery)

Whole-Brain Radiation Therapy (WBRT) RADIATION

Undergo WBRT

Also known as: WBRT, Whole-brain radiotherapy

Arm A (Ipilimumab and Whole Brain Radiation Therapy)

Stereotactic Radiosurgery (SRS) RADIATION

Undergo SRS

Arm B (Ipilimumab and Stereotactic Radiosurgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (2)

Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (60)

• 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.

  PMID: 15325032 BACKGROUND

• 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.

  PMID: 7670677 BACKGROUND

• 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.

  PMID: 9420067 BACKGROUND

• 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.

  PMID: 9809728 BACKGROUND

• 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.

  PMID: 2405271 BACKGROUND

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

  PMID: 18396195 BACKGROUND

• 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.

  PMID: 20425606 BACKGROUND

• 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.

  PMID: 13693470 BACKGROUND

• 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.

  PMID: 19857783 BACKGROUND

• 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.

  PMID: 17133440 BACKGROUND

• 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.

  PMID: 16314647 BACKGROUND

• 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.

  PMID: 18504926 BACKGROUND

• 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.

  PMID: 19652578 BACKGROUND

• 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.

  PMID: 4172540 BACKGROUND

• 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.

  PMID: 16525185 BACKGROUND

• Patchell RA, Regine WF. The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases. Technol Cancer Res Treat. 2003 Apr;2(2):111-5. doi: 10.1177/153303460300200206.

  PMID: 12680791 BACKGROUND

• Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1981 Dec;7(12):1633-8. doi: 10.1016/0360-3016(81)90184-x. No abstract available.

  PMID: 6174490 BACKGROUND

• Chatani M, Matayoshi Y, Masaki N, Inoue T. Radiation therapy for brain metastases from lung carcinoma. Prospective randomized trial according to the level of lactate dehydrogenase. Strahlenther Onkol. 1994 Mar;170(3):155-61.

  PMID: 8160096 BACKGROUND

• Haie-Meder C, Pellae-Cosset B, Laplanche A, Lagrange JL, Tuchais C, Nogues C, Arriagada R. Results of a randomized clinical trial comparing two radiation schedules in the palliative treatment of brain metastases. Radiother Oncol. 1993 Feb;26(2):111-6. doi: 10.1016/0167-8140(93)90091-l.

  PMID: 7681997 BACKGROUND

• Harwood AR, Simson WJ. Radiation therapy of cerebral metastases: a randomized prospective clinical trial. Int J Radiat Oncol Biol Phys. 1977 Nov-Dec;2(11-12):1091-4. doi: 10.1016/0360-3016(77)90114-6. No abstract available.

  PMID: 74375 BACKGROUND

• Kurtz JM, Gelber R, Brady LW, Carella RJ, Cooper JS. The palliation of brain metastases in a favorable patient population: a randomized clinical trial by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1981 Jul;7(7):891-5. doi: 10.1016/0360-3016(81)90005-5. No abstract available.

  PMID: 6171553 BACKGROUND

• Murray KJ, Scott C, Greenberg HM, Emami B, Seider M, Vora NL, Olson C, Whitton A, Movsas B, Curran W. A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104. Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):571-4. doi: 10.1016/s0360-3016(97)00341-6.

  PMID: 9336134 BACKGROUND

• Davey P, Hoegler D, Ennis M, Smith J. A phase III study of accelerated versus conventional hypofractionated whole brain irradiation in patients of good performance status with brain metastases not suitable for surgical excision. Radiother Oncol. 2008 Aug;88(2):173-6. doi: 10.1016/j.radonc.2008.05.020. Epub 2008 Jun 12.

  PMID: 18555546 BACKGROUND

• Mehta MP, Tsao MN, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, Mills M, Rogers CL, Souhami L. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys. 2005 Sep 1;63(1):37-46. doi: 10.1016/j.ijrobp.2005.05.023.

  PMID: 16111570 BACKGROUND

• Meyners T, Heisterkamp C, Kueter JD, Veninga T, Stalpers LJ, Schild SE, Rades D. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis. BMC Cancer. 2010 Oct 26;10:582. doi: 10.1186/1471-2407-10-582.

  PMID: 20977700 BACKGROUND

• Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. doi: 10.1016/S0140-6736(04)16250-8.

  PMID: 15158627 BACKGROUND

• Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7;295(21):2483-91. doi: 10.1001/jama.295.21.2483.

  PMID: 16757720 BACKGROUND

• Pirzkall A, Debus J, Lohr F, Fuss M, Rhein B, Engenhart-Cabillic R, Wannenmacher M. Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases. J Clin Oncol. 1998 Nov;16(11):3563-9. doi: 10.1200/JCO.1998.16.11.3563.

  PMID: 9817276 BACKGROUND

• Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD. Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg. 2003 Feb;98(2):342-9. doi: 10.3171/jns.2003.98.2.0342.

  PMID: 12593621 BACKGROUND

• Powell JW, Chung CT, Shah HR, Canute GW, Hodge CJ, Bassano DA, Liu L, Mitchell L, Hahn SS. Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma. J Neurosurg. 2008 Dec;109 Suppl:122-8. doi: 10.3171/JNS/2008/109/12/S19.

  PMID: 19123898 BACKGROUND

• Lo SS, Clarke JW, Grecula JC, McGregor JM, Mayr NA, Cavaliere R, Kendra KL, Gupta N, Wang JZ, Sarkar A, Olencki TE. Stereotactic radiosurgery alone for patients with 1-4 radioresistant brain metastases. Med Oncol. 2011 Dec;28 Suppl 1:S439-44. doi: 10.1007/s12032-010-9670-5. Epub 2010 Sep 3.

  PMID: 20814764 BACKGROUND

• Nagorsen D, Scheibenbogen C, Marincola FM, Letsch A, Keilholz U. Natural T cell immunity against cancer. Clin Cancer Res. 2003 Oct 1;9(12):4296-303.

  PMID: 14555498 BACKGROUND

• Clemente CG, Mihm MC Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer. 1996 Apr 1;77(7):1303-10. doi: 10.1002/(SICI)1097-0142(19960401)77:73.0.CO;2-5.

  PMID: 8608507 BACKGROUND

• Hakansson A, Gustafsson B, Krysander L, Hakansson L. Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment. Br J Cancer. 1996 Sep;74(5):670-6. doi: 10.1038/bjc.1996.420.

  PMID: 8845294 BACKGROUND

• Mihm MC Jr, Clemente CG, Cascinelli N. Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab Invest. 1996 Jan;74(1):43-7.

  PMID: 8569196 BACKGROUND

• Moschos SJ, Edington HD, Land SR, Rao UN, Jukic D, Shipe-Spotloe J, Kirkwood JM. Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol. 2006 Jul 1;24(19):3164-71. doi: 10.1200/JCO.2005.05.2498.

  PMID: 16809739 BACKGROUND

• Peggs KS, Quezada SA, Korman AJ, Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol. 2006 Apr;18(2):206-13. doi: 10.1016/j.coi.2006.01.011. Epub 2006 Feb 7.

  PMID: 16464564 BACKGROUND

• Tarhini AA, Iqbal F. CTLA-4 blockade: therapeutic potential in cancer treatments. Onco Targets Ther. 2010 Jun 24;3:15-25. doi: 10.2147/ott.s4833.

  PMID: 20616954 BACKGROUND

• Robert C, Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist. 2009 Aug;14(8):848-61. doi: 10.1634/theoncologist.2009-0028. Epub 2009 Aug 1.

  PMID: 19648604 BACKGROUND

• Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000 Jul 17;192(2):295-302. doi: 10.1084/jem.192.2.295.

  PMID: 10899916 BACKGROUND

• Kaehler KC, Piel S, Livingstone E, Schilling B, Hauschild A, Schadendorf D. Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. Semin Oncol. 2010 Oct;37(5):485-98. doi: 10.1053/j.seminoncol.2010.09.003.

  PMID: 21074064 BACKGROUND

• Morse MA. Technology evaluation: ipilimumab, Medarex/Bristol-Myers Squibb. Curr Opin Mol Ther. 2005 Dec;7(6):588-97.

  PMID: 16370382 BACKGROUND

• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.

  PMID: 20525992 BACKGROUND

• Weber JS, O'Day S, Urba W, Powderly J, Nichol G, Yellin M, Snively J, Hersh E. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol. 2008 Dec 20;26(36):5950-6. doi: 10.1200/JCO.2008.16.1927. Epub 2008 Nov 17.

  PMID: 19018089 BACKGROUND

• Schartz NE, Farges C, Madelaine I, Bruzzoni H, Calvo F, Hoos A, Lebbe C. Complete regression of a previously untreated melanoma brain metastasis with ipilimumab. Melanoma Res. 2010 Jun;20(3):247-50. doi: 10.1097/CMR.0b013e3283364a37.

  PMID: 20216240 BACKGROUND

• Hodi FS, Oble DA, Drappatz J, Velazquez EF, Ramaiya N, Ramakrishna N, Day AL, Kruse A, Mac Rae S, Hoos A, Mihm M. CTLA-4 blockade with ipilimumab induces significant clinical benefit in a female with melanoma metastases to the CNS. Nat Clin Pract Oncol. 2008 Sep;5(9):557-61. doi: 10.1038/ncponc1183. Epub 2008 Jul 29.

  PMID: 18665147 BACKGROUND

• Pilones KA, Kawashima N, Yang AM, Babb JS, Formenti SC, Demaria S. Invariant natural killer T cells regulate breast cancer response to radiation and CTLA-4 blockade. Clin Cancer Res. 2009 Jan 15;15(2):597-606. doi: 10.1158/1078-0432.CCR-08-1277.

  PMID: 19147765 BACKGROUND

• Jaber SH, Cowen EW, Haworth LR, Booher SL, Berman DM, Rosenberg SA, Hwang ST. Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent. Arch Dermatol. 2006 Feb;142(2):166-72. doi: 10.1001/archderm.142.2.166.

  PMID: 16490844 BACKGROUND

• Robinson MR, Chan CC, Yang JC, Rubin BI, Gracia GJ, Sen HN, Csaky KG, Rosenberg SA. Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis. J Immunother. 2004 Nov-Dec;27(6):478-9. doi: 10.1097/00002371-200411000-00008.

  PMID: 15534492 BACKGROUND

• Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, Korman A, Lautz D, Russell S, Jaklitsch MT, Ramaiya N, Chen TC, Neuberg D, Allison JP, Mihm MC, Dranoff G. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3005-10. doi: 10.1073/pnas.0712237105. Epub 2008 Feb 19.

  PMID: 18287062 BACKGROUND

• Downey SG, Klapper JA, Smith FO, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Allen TE, Levy CL, Yellin M, Nichol G, White DE, Steinberg SM, Rosenberg SA. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6681-8. doi: 10.1158/1078-0432.CCR-07-0187. Epub 2007 Nov 2.

  PMID: 17982122 BACKGROUND

• Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol. 2008 Feb 1;26(4):527-34. doi: 10.1200/JCO.2007.12.7837.

  PMID: 18235113 BACKGROUND

• Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, Begg CB, Agarwala SS, Schuchter LM, Ernstoff MS, Houghton AN, Kirkwood JM. Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol. 1999 Sep;17(9):2745-51. doi: 10.1200/JCO.1999.17.9.2745.

  PMID: 10561349 BACKGROUND

• Middleton MR, Lorigan P, Owen J, Ashcroft L, Lee SM, Harper P, Thatcher N. A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma. Br J Cancer. 2000 Mar;82(6):1158-62. doi: 10.1054/bjoc.1999.1056.

  PMID: 10735499 BACKGROUND

• Bedikian AY, Millward M, Pehamberger H, Conry R, Gore M, Trefzer U, Pavlick AC, DeConti R, Hersh EM, Hersey P, Kirkwood JM, Haluska FG; Oblimersen Melanoma Study Group. Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J Clin Oncol. 2006 Oct 10;24(29):4738-45. doi: 10.1200/JCO.2006.06.0483. Epub 2006 Sep 11.

  PMID: 16966688 BACKGROUND

• van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999 Aug 2;190(3):355-66. doi: 10.1084/jem.190.3.355.

  PMID: 10430624 BACKGROUND

• Suh JH, Videtic GM, Aref AM, Germano I, Goldsmith BJ, Imperato JP, Marcus KJ, McDermott MW, McDonald MW, Patchell RA, Robins HI, Rogers CL, Wolfson AH, Wippold FJ 2nd, Gaspar LE. ACR Appropriateness Criteria: single brain metastasis. Curr Probl Cancer. 2010 May-Jun;34(3):162-74. doi: 10.1016/j.currproblcancer.2010.04.003.

  PMID: 20541055 BACKGROUND

• Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, Farnan N. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):291-8. doi: 10.1016/s0360-3016(99)00507-6.

  PMID: 10802351 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Williams NL, Wuthrick EJ, Kim H, Palmer JD, Garg S, Eldredge-Hindy H, Daskalakis C, Feeney KJ, Mastrangelo MJ, Kim LJ, Sato T, Kendra KL, Olencki T, Liebner DA, Farrell CJ, Evans JJ, Judy KD, Andrews DW, Dicker AP, Werner-Wasik M, Shi W. Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases. Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):22-30. doi: 10.1016/j.ijrobp.2017.05.028. Epub 2017 May 26.

  PMID: 28816150 DERIVED

Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Ipilimumab; Radiosurgery

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Wenyin Shi
• Organization: Sidney Kimmel Cancer Center at Thomas Jefferson University

Wenyin.Shi@jefferson.edu

215-955-6702

Study Officials

• Wenyin Shi, MD, PhD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2012
• First Posted: October 10, 2012
• Study Start: November 9, 2012
• Primary Completion: May 20, 2015
• Study Completion: April 11, 2018
• Last Updated: May 16, 2025
• Results First Posted: August 19, 2019

Record last verified: 2025-05

Locations

US (2)