A Randomized Phase 2 Trial of Ipilumumab and Nivolumab With or Without Hypofractionated Radiotherapy in Patients With Metastatic Melanoma

Abramson Cancer Center at Penn Medicine3 sites in 1 country54 target enrollmentNovember 27, 2018

ConditionsMetastatic Melanoma

InterventionsNivolumab Ipilimumab Hypofractionated Radiation Therapy (HFRT)

DrugsNivolumab Ipilimumab

Overview

Phase: Phase 2
Intervention: Nivolumab
Conditions: Metastatic Melanoma
Sponsor: Abramson Cancer Center at Penn Medicine
Enrollment: 54
Locations: 3
Primary Endpoint: Number of Adverse Events
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

November 27, 2018

End Date

December 31, 2027

Last Updated

8 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Abramson Cancer Center at Penn Medicine

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed metastatic melanoma.
•Have at least two measurable lesions (including the index lesion) according to RECIST (Response Evaluation Criteria in Solid Tumours)guidelines v1.
•Have an index lesion measuring between 1cm - 7cm that is amenable to hypofractionated radiation therapy (HFRT) 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 Principal Investigator (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.

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-programmed death ligand (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. Prior adjuvant PD-1 blockade (but not prior adjuvant Cytotoxic T lymphocyte-associated antigen (CTLA)-4 blockade) is permitted.
•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.