Clinical Trials /

Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma

NCT03646617

Description:

The main purpose of this study is to determine the safety of combining ipilimumab and nivolumab with hypofractionated radiotherapy to a single tumor in patients with metastatic melanoma. Another purpose of this study is to determine the effect of ipilimumab, nivolumab and hypofractionated radiotherapy on the cancer as compared to ipilimumab and nivolumab.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma
  • Official Title: A Randomized Phase 2 Trial of Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: UPCC 05618
  • SECONDARY ID: 829922
  • NCT ID: NCT03646617

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
NivolumabNo HFRT
IpilimumabNo HFRT

Purpose

The main purpose of this study is to determine the safety of combining ipilimumab and nivolumab with hypofractionated radiotherapy to a single tumor in patients with metastatic melanoma. Another purpose of this study is to determine the effect of ipilimumab, nivolumab and hypofractionated radiotherapy on the cancer as compared to ipilimumab and nivolumab.

Trial Arms

NameTypeDescriptionInterventions
No HFRTActive Comparatoripilimumab and nivolumab once every 3 weeks for up to 4 doses, followed by nivolumab once every 2 weeks until disease progression.
  • Nivolumab
  • Ipilimumab
HFRTExperimentalThe dose of HFRT will be 8 Gy x 3 fractions, given over a maximum of 7 days timespan.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed metastatic melanoma.

          -  Have at least two measurable lesions (including the index lesion) according to RECIST
             guidelines v1.1.

          -  Have an index lesion measuring between 1cm - 7cm that is amenable to HFRT radiation
             therapy at the discretion of the treating radiation oncologist

          -  Able to tolerate HFRT (e.g. lie flat and hold position for treatment)

          -  Able to provide signed, written informed consent and age > 18 years at time of signing

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  Recovery from the adverse effects of prior cancer treatments, defined as effects
             having resolved to NCI CTCAE v5 Grade 1 or better with the exception of alopecia.
             Subjects with irreversible toxicity that is not reasonably expected to be exacerbated
             by nivolumab and ipilimumab may be included (eg, hearing loss, neuropathy) upon
             approval of the PI.

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential must be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for two weeks
             before the time of the first dose of study medication, while on study, through 120
             days after the last dose of study medication. Subjects of childbearing potential are
             those who have not been surgically sterilized or have not been free from menses for >
             1 year.

          -  Non-sterilized male subjects must agree to use an adequate method of contraception
             starting with the first dose of study therapy through 120 days after the last dose of
             study therapy. Acceptable forms of birth control include condoms, diaphragms, cervical
             cap, an intra-uterine device (IUD), surgical sterility (tubal ligation or a partner
             that has undergone a vasectomy), or oral contraceptives, OR the subject must agree to
             completely abstain from heterosexual intercourse. Abstinence at certain times of the
             cycle only, such as during the days of ovulation, after ovulation and withdrawal are
             not acceptable methods of birth control.

          -  Demonstrate adequate organ function; all screening labs should be performed within 21
             days of date of consent.

          -  White blood cell >= 2,500 cells/ul

          -  Absolute neutrophil count (ANC) ≥1,500 /mcL

          -  Platelets >=100,000 / mcL

          -  Hemoglobin >=9 g/dL

          -  Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used
             in place of creatinine or CrCl) <=1.5 X upper limit of normal (ULN) OR >=60 mL/min for
             subject with creatinine levels > 1.5 X institutional ULN (Creatinine clearance should
             be calculated per institutional standard.)

          -  Serum total bilirubin <= 1.5 X ULN OR

          -  Direct bilirubin <= ULN for subjects with total bilirubin levels > 1.5 ULN

          -  AST (SGOT) and ALT (SGPT) <= 2.5 X ULN OR <= 5 X ULN for subjects with liver
             metastases

        Exclusion Criteria:

          -  Central nervous system (CNS) metastases requiring urgent local therapy; patients with
             carcinomatous meningitis are excluded. If there is clinical suspicion of brain
             metastases, a brain MRI should be obtained.

          -  Concurrent enrollment in another clinical study, unless in a follow-up period or the
             study is an observational or non-interventional study.

          -  Prior therapy with an anti-PD-1 (including nivolumab), anti-PD-L1, anti-PDL2, or
             anti-CTLA4 (including ipilimumab) agents, interferon, HD IL-2 or any other antibody or
             drug specifically targeting T-cell co-stimulation or checkpoint pathways.

          -  Concurrent treatment with any anticancer agent, including chemotherapy, immunotherapy,
             or biologic therapy.

          -  Treatment with any other investigational agent within 4 weeks prior to first dose of
             nivolumab/ipilimumab.

          -  Prior chemotherapy, targeted small molecule therapy or other anti-cancer therapy
             within 2 weeks prior to first dose of nivolumab/ipilimumab or who has not recovered
             (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered
             agent.

        Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify
        for the study.

          -  Known hypersensitivity to nivolumab, ipilimumab, monoclonal antibodies or
             immunoglobulin G.

          -  Major surgical procedure (as defined by the investigator) within 28 days prior to the
             first dose of nivolumab/ipilimumab or still recovering from prior surgery

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of nivolumab/ipilimumab with the exceptions of intranasal, topical and inhaled
             corticosteroids, systemic corticosteroids at physiologic doses not to exceed 10 mg/day
             of prednisone or equivalent, or steroids used transiently to control contrast agent
             allergies for radiographic studies.

          -  Active or prior documented autoimmune disease (including inflammatory bowel disease,
             diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel
             disease, Wegner syndrome, Hashimoto syndrome) within the past year. Subjects with
             vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment
             (within the past year) are not excluded. Patients with hypothyroidism stable on
             thyroid replacement therapy for the previous 3 months are not excluded.

          -  History of primary immunodeficiency or tuberculosis.

          -  Known true positive results for HIV or known active Hepatitis B (e.g. HBsAg reactive)
             or Hepatitis C (e.g. HCV RNA [qualitative] is detected) as determined by medical
             record review.

          -  Receipt of a live, attenuated vaccine within 28 days prior to the first dose of
             nivolumab/ipilimumab. (NOTE: subjects, if enrolled, should not receive live vaccine
             during the study or for 180 days after the last dose of both drugs)

          -  Clinical contraindication to hypofractionated radiation as determined by the
             investigator (e.g., active systemic sclerosis, active inflammatory bowel disease if
             bowel is within radiation field.)

          -  Prior radiotherapy that precludes the proposed treatment with HFRT or any radiotherapy
             within 28 days of first dose of nivolumab/ipilimumab.

          -  Females who are pregnant, lactating, or intend to become pregnant during the
             participation of the study.

          -  Uncontrolled inter-current illness, including, but not limited to, ongoing or active
             infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled
             hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease,
             or psychiatric illness/social situations that would limit compliance with study
             requirement or compromise the ability of the subject to give written informed consent

          -  Other active invasive malignancy. History of non-invasive malignancies such as
             cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal
             carcinoma in situ of the breast is allowed, as is history of other invasive malignancy
             that is in remission after treatment with curative intent.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of the investigational product or interpretation of subject safety or study
             results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:3.5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:progression-free survival
Time Frame:3.5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

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