A Pilot Study of Ipilumimab and Radiation in Poor Prognosis Melanoma

NCT01996202 | Completed Phase 1 DMC

• 1 other identifier: Pro00045042
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study assessing the safety of the combination of ipilimumab administered concurrently with radiotherapy for patients with locally advanced or unresectable melanoma and patients at high risk for recurrence after resection.

Conditions

High Risk Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (2)

• Incidence of immune related adverse events associated with ipilimumab

  2 years

• Incidence of acute and late radiation toxicities

  2 years

Secondary Outcomes (6)

• Overall response rate (ORR)

  2 years

• 6 month progression free survival (PFS)

  6 months

• 12 month progression free survival (PFS)

  12 months

• Overall survival

  2 years

• CD4+ and CD8+ reactivity to melanoma tumor antigens

  2 years

Study Arms (2)

Resected Melanoma

OTHER

Subjects with resected melanoma.

Drug: Ipilumimab; Radiation: Radiation

Unresected Melanoma

OTHER

Subjects with unresected melanoma.

Drug: Ipilumimab; Radiation: Radiation

Interventions

Ipilumimab DRUG

Resected Melanoma; Unresected Melanoma

Radiation RADIATION

Resected Melanoma; Unresected Melanoma

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give written informed consent.
• Histologic diagnosis of melanoma
• Cohort 1: Resected patients at high risk of recurrence. Patients must meet at least one of the following criteria
• a. Melanoma of mucosal origin b. Desmoplastic melanoma c. Primary melanoma of the head or neck with any lymph node involvement d. Patients with non-head and neck primaries must have had preoperative/pathologic macroscopic lymph node involvement, defined by clinically evident on exam or imaging evaluation, plus at least one of the following by clinical, imaging, or pathologic evaluation: i. ≥ 2 cervical or axillary nodes ii. ≥ 3 groin lymph nodes iii. Extracapsular extension (ECE) of tumor iv. Lymph nodes ≥ 3cm
• Cohort 2: Neoadjuvant/definitive approach for locally advanced patients. Patients must meet at least one of the following criteria
• Melanoma of mucosal origin
• Desmoplastic melanoma
• Patients with radiographic evidence of tumor invasion into surrounding local structures rendering them inoperable
• Macroscopic nodal involvement. In addition, patients must also meet one of the following criteria
• i. Recurrent disease, with any number and size of nodes ii. ≥ 1 parotid node(s) iii. ≥ 2 cervical or axillary nodes iv. ≥ 3 groin lymph nodes v. Lymph nodes ≥ 3cm vi. ECE of tumor
• Resected patients should begin treatment within 12 weeks of surgery, once adequately healed as determined by the treating physicians.
• Local-regional treatment sites must be able to be encompassed within a reasonable radiation therapy treatment volume
• Patients with recurrent disease are allowed in cohort 1, provided at least one of the criteria listed in 3 above is met
• For patients with a new diagnosis of melanoma treated in cohort 2 who have a cutaneous primary, the primary site may be addressed surgically (wide local excision; skin grafting) prior to the initiation of ipilimumab and radiation at the discretion of the treating surgeon.
• Required values for initial laboratory tests:

You may not qualify if:

• Ocular melanoma
• Presence of brain metastases
• Prior radiation therapy for melanoma
• Any other malignancy form which the patient has been disease-free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or DCIS. Patients with prior malignancies that are not considered to be an active problem may be enrolled at the discretion of the investigator, regardless of time frame.
• 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).
• Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab 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 1 month before or after any dose of ipilimumab).
• A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist.
• 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 in the previous 4 weeks (defined as prednisone 10mg daily or equivalent.)
• Women of childbearing potential (WOCBP), defined above in Section 4.1, who:
• are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
• have a positive pregnancy test at baseline, or
• are pregnant or breastfeeding.
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness.
• Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped. Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Radiation

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

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: November 22, 2013
• First Posted: November 27, 2013
• Study Start: November 1, 2013
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: July 5, 2019

Record last verified: 2019-07

Locations

US (1)