- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02107755
Stereotactic Radiation Therapy and Ipilimumab in Treating Patients With Metastatic Melanoma
A Phase 2 Study Using Stereotactic Ablative Radiation Therapy and Ipilimumab in Patients With Oligometastatic Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Ohio State University Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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
- 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
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
- 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
- A visceral metastasis that due to its location cannot be safely treated with SABR
Women of childbearing potential (WOCBP), defined above who:
- Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 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
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
- Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (ipilimumab, stereotactic radiosurgery)
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.
|
Given IV
Other Names:
Undergo stereotactic radiosurgery
Blood and tissue samples will be collected for research purposes.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Time of study enrollment until the first documented date of disease progression, assessed up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of progression-free survival by irRC 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.
|
Time of study enrollment until the first documented date of disease progression, assessed up to 6 months
|
Frequency of grade 3 and grade 4 toxicities according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4
Time Frame: Up to 90 days after the last ipilimumab infusion
|
Frequency and severity of adverse events and tolerability of the regimen in each of the patient groups will be collected and summarized by descriptive statistics.
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
|
Up to 90 days after the last ipilimumab infusion
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Frequency of objective response rate, defined as complete response + partial response, measured by computed tomography (CT) using mWHO criteria
Time Frame: Up to 12 weeks
|
Up to 12 weeks
|
|
Frequency of objective response rate, defined using irRC
Time Frame: Up to 12 weeks
|
Up to 12 weeks
|
|
Rate of local failure
Time Frame: Time of study enrollment until the first documented date of failure within the irradiated field, assessed up to 10 years
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Time of study enrollment until the first documented date of failure within the irradiated field, assessed up to 10 years
|
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Rate of overall survival
Time Frame: Time of study enrollment until the time of death, assessed up to 10 years
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Kaplan-Meier curves will be used.
|
Time of study enrollment until the time of death, assessed up to 10 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in marker levels between those with vs. without the clinical improvement
Time Frame: Baseline to week 50
|
Summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g.
prog-free and alive at 6 months vs. not).
Graphical analyses will be largely used to assess potential patterns and relationships; e.g.
side-by-side boxplots to assess differences.
|
Baseline to week 50
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jose Bazan, MD, Ohio State University
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neoplastic Processes
- Neuroendocrine Tumors
- Nevi and Melanomas
- Neoplasm Metastasis
- Melanoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Antibodies
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Ipilimumab
Other Study ID Numbers
- OSU-12182
- NCI-2014-00381 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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