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Metastatic MelanomaPhase 2RadVaxNCT03646617

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

A Phase 2 study testing Hypofractionated Radiation Therapy (HFRT), Nivolumab and Ipilimumab in people with Metastatic Melanoma, run by Abramson Cancer Center at Penn Medicine at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
Hypofractionated Radiation Therapy (HFRT), Nivolumab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
3 sitesUnited States
Study dates
27 Nov 2018to 31 Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Histologically confirmed metastatic melanoma.
  • Have at least two measurable lesions (including the index lesion) according to RECIST (Response Evaluation Criteria in Solid Tumours)guidelines v1.1.
  • 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
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  • 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.
  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17601

  • Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Huntsman Cancer Institute at the University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

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

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.

Being tested
Hypofractionated Radiation Therapy (HFRT), Nivolumab, Ipilimumab
Medical subject headings
Melanoma

What participants receive

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

  • Hypofractionated Radiation Therapy (HFRT)Radiation

    The dose of HFRT will be 8 Gy x 3 fractions, given over a maximum of 7 days timespan.

  • NivolumabDrug

    Nivolumab (1 mg/kg) will be administered as an IV infusion over 30 minutes, followed by ipilimumab (3 mg/kg) on the same day given as an IV infusion over 90 minutes. The two drugs will be given on day 1, then every 3 weeks for a total of four doses. After these 4 doses, the patient and investigator will decide to continue with nivolumab (240 mg) every 2 weeks or Nivolumab (480mg) every 4 weeks as monotherapy for up to one year as an IV infusion over 30 minutes.

  • IpilimumabDrug

    Nivolumab (1 mg/kg) will be administered as an IV infusion over 30 minutes, followed by ipilimumab (3 mg/kg) on the same day given as an IV infusion over 90 minutes. The two drugs will be given on day 1, then every 3 weeks for a total of four doses.

Study groups in NCT03646617
Study groupRoleWhat they receive
No HFRTActive comparatoripilimumab and nivolumab once every 3 weeks for up to 4 doses, followed by nivolumab once every 2 weeks or every 4 weeks until disease progression.
Receives: Drug: Nivolumab; Drug: Ipilimumab
HFRTExperimentalThe dose of hypofractionated radiation therapy (HFRT) will be 8 Gy x 3 fractions, given over a maximum of 7 days timespan.
Receives: Radiation: Hypofractionated Radiation Therapy (HFRT); Drug: Nivolumab; Drug: Ipilimumab

What is being measured

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

  1. Number of Adverse Events

    Measured: 3.5 years

Secondary outcomes (1)

  1. progression-free survival

    Measured: 3.5 years

Timeline

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

  1. First posted24 Aug 2018
  2. Study start27 Nov 2018
  3. Primary completion21 Mar 2026
  4. Study completion31 Dec 2027 (estimated)

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03646617
Sponsor's protocol ID
UPCC 05618
Other IDs
829922, 5P01CA210944-05
Acronym
RadVax
Status last verified
Aug 2026
First submitted
23 Aug 2018
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hypofractionated Radiation Therapy (HFRT), Nivolumab and Ipilimumab in people with Metastatic Melanoma, run by Abramson Cancer Center at Penn Medicine at 3 sites 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 20 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: under way, not looking for participants, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

This study is still under way. Results are not available in the source record yet.

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?

Number of Adverse Events (time frame: 3.5 years). 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 NCT03646617.

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 17 Aug 2026.

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