A Phase 2 Study Using Stereotactic Ablative Radiation Therapy and Ipilimumab in Patients With Oligometastatic Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Liver Metastases
- Sponsor
- Ohio State University Comprehensive Cancer Center
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Rate of Progression-free Survival by mWHO Criteria
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the progression-free survival of patients with oligometastatic melanoma treated with the combination of stereotactic ablative radiation therapy (SABR) (stereotactic radiosurgery) and ipilimumab in patients with oligometastatic melanoma using modified World Health Organization (mWHO) criteria. SECONDARY OBJECTIVES: I. To evaluate the 6-month progression-free survival of the combination of SABR and 3 mg/kg ipilimumab in patients with oligometastatic melanoma using immune related response criteria (irRC) criteria. II. To evaluate the tolerability and safety of the combination. III. To evaluate the response rate based on mWHO \& irRC criteria. IV. To evaluate the local control rate. V. To evaluate the overall survival rate. TERTIARY OBJECTIVES: I. Evaluate changes in blood and serum markers: absolute lymphocyte count, T-cell activation markers, T-cell suppression markers, T-helper cells and related cytokines, T-regulatory (T-reg) markers, co-stimulatory molecules, and serum cytokines when SABR is added to the ipilimumab regimen. II. Evaluate genomic deoxyribonucleic acid (DNA) mutations in key melanoma genes and their correlation with response, progression-free survival, and overall survival. OUTLINE: Patients receive ipilimumab intravenously (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. After completion of study treatment, patients are followed up at 30 and 90 days, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
- •1-3 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
Exclusion Criteria
- •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
Outcomes
Primary Outcomes
Rate of Progression-free Survival by mWHO Criteria
Time Frame: Time of study enrollment until the first documented date of disease progression, assessed up to 6 months
Calculated along with corresponding 95% binomial confidence intervals. Kaplan-Meier curves will be used.
Secondary Outcomes
- Frequency of Objective Response Rate, Defined Using irRC(Up to 12 weeks)
- 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)
- Rate of Local Failure(Time of study enrollment until the first documented date of failure within the irradiated field, assessed up to 10 years)
- Rate of Overall Survival(Time of study enrollment until the time of death, assessed up to 6 years)
- 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)
- Frequency of Objective Response Rate, Defined as Complete Response + Partial Response, Measured by Computed Tomography (CT) Using mWHO Criteria(Up to 12 weeks)