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Liver MetastasesPhase 2NCT02107755

Stereotactic Radiation Therapy and Ipilimumab in Treating Patients With Metastatic Melanoma

A Phase 2 study testing ipilimumab, stereotactic radiosurgery and laboratory biomarker analysis in people with Liver Metastases and Lung Metastases, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ipilimumab, stereotactic radiosurgery and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
5 Sep 2014to 16 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase 2 Study Using Stereotactic Ablative Radiation Therapy and Ipilimumab in Patients With Oligometastatic Melanoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
ipilimumab, stereotactic radiosurgery, laboratory biomarker analysis
Keywords
oligometastatic melanoma, melanoma
Medical subject headings
Melanoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ipilimumabBiological

    Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

    Given IV

  • stereotactic radiosurgeryRadiation

    Undergo stereotactic radiosurgery

  • laboratory biomarker analysisOther

    Blood and tissue samples will be collected for research purposes.

Study groups in NCT02107755
Study groupRoleWhat they receive
Treatment (ipilimumab, stereotactic radiosurgery)ExperimentalPatients 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.
Receives: Biological: ipilimumab; Radiation: stereotactic radiosurgery; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Progression-free Survival by mWHO Criteria

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

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

Secondary outcomes (6)

  1. Rate of Progression-free Survival by irRC Criteria

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

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

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

    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.

    Measured: Up to 90 days after the last ipilimumab infusion

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

    The response rate evaluated based on mWHO \& irRC criteria

    Measured: Up to 12 weeks

  4. Frequency of Objective Response Rate, Defined Using irRC

    Measured: Up to 12 weeks

  5. Rate of Local Failure

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

  6. Rate of Overall Survival

    Kaplan-Meier curves will be used.

    Measured: Time of study enrollment until the time of death, assessed up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2014 (estimated)
  2. Study start5 Sep 2014
  3. Primary completion3 Aug 2020
  4. Study completion16 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02107755
Sponsor's protocol ID
OSU-12182
Other IDs
NCI-2014-00381
Status last verified
Apr 2024
First submitted
4 Apr 2014
Last updated
21 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ipilimumab, stereotactic radiosurgery and laboratory biomarker analysis in people with Liver Metastases and Lung Metastases, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02107755.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024.

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