Stereotactic Radiation Therapy and Ipilimumab in Treating Patients With Metastatic Melanoma

NCT02107755 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: OSU-12182NCI-2014-00381
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effectiveness of the combination of stereotactic radiation therapy and ipilimumab in patients with metastatic melanoma that has spread to four or fewer sites in the body (oligometastatic). Stereotactic radiation therapy is a type of external beam radiation therapy that uses special equipment to position the patient and precisely give a either a single large dose of radiation therapy to a tumor or several large doses of radiation therapy to a tumor using precision and accuracy that is guided by onboard daily imaging prior to radiation therapy. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some monoclonal antibodies find tumor cells and help kill them or carry tumor-killing substances to them. Giving stereotactic radiosurgery together with ipilimumab may kill more tumor cells by causing addition melanoma antigens to be presented to the immune system.

Conditions

Liver Metastases; Lung Metastases; Recurrent Melanoma; Stage IV Melanoma; Tumors Metastatic to Brain

Keywords

oligometastatic melanoma; melanoma

Outcome Measures

Primary Outcomes (1)

• Rate of Progression-free Survival by mWHO Criteria

  Calculated along with corresponding 95% binomial confidence intervals. Kaplan-Meier curves will be used.

  Time of study enrollment until the first documented date of disease progression, assessed up to 6 months

Secondary Outcomes (6)

• Rate of Progression-free Survival by irRC Criteria

  Time of study enrollment until the first documented date of disease progression, assessed up to 6 months

• Number of Participants With Grade 3 and Grade 4 Toxicities According to Common Toxicity Criteria for Adverse Events (CTCAE) Version 4

  Up to 90 days after the last ipilimumab infusion

• Frequency of Objective Response Rate, Defined as Complete Response + Partial Response, Measured by Computed Tomography (CT) Using mWHO Criteria

  Up to 12 weeks

• Frequency of Objective Response Rate, Defined Using irRC

  Up to 12 weeks

• Rate of Local Failure

  Time of study enrollment until the first documented date of failure within the irradiated field, assessed up to 10 years

Other Outcomes (1)

• Change in Marker Levels Between Those With vs. Without the Clinical Improvement

  Baseline to week 50

Study Arms (1)

Treatment (ipilimumab, stereotactic radiosurgery)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes on day 1 in weeks 1, 4, 7, and 10. Treatment repeats every 3 weeks for up to 4 total doses in the absence of disease progression or unacceptable toxicity. At approximately 5-6 weeks, patients undergo stereotactic radiosurgery over 2-3 days per week. Patients with stable disease or confirmed partial or complete response after completion of ipilimumab therapy at week 12 may receive re-induction ipilimumab at the discretion of the treating physician.

Biological: ipilimumab; Radiation: stereotactic radiosurgery; Other: laboratory biomarker analysis

Interventions

ipilimumab BIOLOGICAL

Given IV

Also known as: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

Treatment (ipilimumab, stereotactic radiosurgery)

stereotactic radiosurgery RADIATION

Undergo stereotactic radiosurgery

Treatment (ipilimumab, stereotactic radiosurgery)

laboratory biomarker analysis OTHER

Blood and tissue samples will be collected for research purposes.

Treatment (ipilimumab, stereotactic radiosurgery)

Eligibility Criteria

• Age: 18 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
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Histologic diagnosis of melanoma with metastatic disease to a visceral organ (lung, liver, brain, adrenal, nodal station outside the regional lymph drainage of the primary, vertebral bodies)
• sites of metastatic disease able to be targeted by SABR
• White blood cells (WBC) \>= 2000/uL
• Absolute neutrophil count (ANC) \>= 1000/uL
• Platelets \>= 75 x 10\^3/uL
• Hemoglobin \>= 9 g/dL (\>= 80 g/L; may be transfused)
• Creatinine =\< 2.0 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN for patients without liver metastasis, =\< 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)
• No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• 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

You may not qualify if:

• Any other malignancy from 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 or carcinoma in situ of the cervix
• 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 adverse events (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 cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist
• A history of prior treatment with anti-programmed death (PD)-1 or anti-PD-L1 antibodies
• Concomitant therapy with any of the following: interleukin (IL)-2, interferon, other non-study immunotherapy regimens, cytotoxic chemotherapy, other investigation therapies
• Concomitant therapy with immune-suppressants or chronic use of systemic corticosteroids
• Must be off prior systemic therapies for 2 weeks prior to enrollment; patients that have been previously treated with systemic therapy adjuvantly or for metastatic disease remain eligible as long as they continue to meet all other eligibility criteria (oligometastatic, no visceral metastasis \> 5 cm, eligible for SABR)
• Prior radiation therapy that at the treating physician's discretion makes SABR unsafe
• No evidence of pleural effusion or ascites
• Congestive heart failure \> class II New York Heart Association (NYHA) or unstable angina
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Major surgery, open biopsy or significant traumatic injury within 2 weeks of first dose of study drug
• A visceral metastasis greater than 5 cm

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; 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; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Dr. Jose Bazan
• Organization: The Ohio State University Comprehensive Cancer Center

Jose.Bazan2@osumc.edu

614-688-7040

Study Officials

• Jose Bazan, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 8, 2014
• Study Start: September 5, 2014
• Primary Completion: August 3, 2020
• Study Completion: August 16, 2021
• Last Updated: May 21, 2024
• Results First Posted: May 21, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)