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Metastatic MelanomaPhase 1/2NCT03297463

Radiation Therapy With Combination Immunotherapy for Relapsed/Refractory Metastatic Melanoma

A Phase 1/2 study testing Interleukin-2 & Ipilimumab (P-Ib) and Interleukin-2 & Ipilimumab (P-II) in people with Metastatic Melanoma and Pulmonary Metastases, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a Phase 1b/2 study designed to evaluate combination of the human T-cell cytokine Interleukin-2 (IL-2) and a checkpoint inhibitor Ipilimumab immediately following a course of hypofractionated palliative radiation therapy in the management of unresectable, relapsed/refractory metastatic melanoma. Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Interleukin-2 & Ipilimumab (P-Ib) and Interleukin-2 & Ipilimumab (P-II)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
31 Jan 2018to 1 Feb 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Biopsy-proven unresectable, metastatic melanoma refractory to standard immunotherapy drugs or regimens, including prior treatment with Aldesleukin (IL-2), GM-CSF, Ipilimumab, Nivolumab, Pembrolizumab, and/or Imlygic (T-VEC).
  • Prior clinical trial participation or treatment with molecularly targeted agents (i.e. Vemurafenib/Cobimetinib, Dabrafenib/Trametinib) or chemotherapy (i.e. Temozolomide, Dacarbazine, Platinum, or Taxanes) is permitted.
  • Must have a minimum of 3 radiographically distinct (>1.5 cm) lesions measurable by RECIST 1.1 at time of study enrollment (>5 preferred).
  • A maximum of 2 metastases per treated organ may be targeted for HD-XRT, but must be separated by more than 5 cm of normal tissue
  • At least 2 non-irradiated lesions are required for systemic response assessments
  • Pulmonary metastases: Pulmonary metastasis permissible. Appropriate candidates with lung lesions may be considered for ablative hypofractionation using SBRT.
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  • Hepatic metastases: Hepatic metastasis permissible. Appropriate candidates with metastasis to liver may be considered for ablative hypofractionation using SBRT.
  • Brain metastases: Brain metastases may be treated using Gamma Knife Radiosurgery (GKR) or whole brain radiation therapy (WBRT) per the treating radiation oncologist. Total radiation dose and number of fractions will be determined by the treating radiation oncologist based on anatomic and dosing constraints. MRI of the vertebral column is required for all patients with suspected epidural tumor extension.
  • Must have sufficient archival tissue block material (1.5 x 1.5 x 1.5 cm) and/or newly obtained core or excisional biopsy of tumor tissue; minimum of 2 cores.
  • ECOG performance status 0 or 1 (appendix 2)
  • Age 18 to 85 years of age; > 85 years of age must be approved by Principal Investigator.
  • Adequate organ function within 14 days of registration (30 days for pulmonary and cardiac assessments) defined as:
  • Hematologic: Leukocytes ≥ 3,000/mcL, ANC ≥ 1,000/mcL, Hemoglobin ≥ 9.0 g/dL, Platelets ≥ 120,000/mcL
  • Renal: Serum creatinine ≤ 1.8 mg/dL; for patients with a creatinine > 1.5 mg/dL or a history of renal dysfunction, an estimated glomerular filtration rate ≥ 35 mL/min/1.73 m2 is required
  • Hepatic: AST, ALT, and alkaline phosphatase ≤ 10 x upper limit of normal and total bilirubin ≤ 2.0 mg/dL Pulmonary: oxygen saturation ≥90% on room air; corrected DLCO and FEV1, ≥ 50% predicted
  • Cardiac: Absence of clinical decompensated congestive heart failure or uncontrolled arrhythmia; left ventricular ejection fraction (echocardiogram within 6 months permitted) ≥ 40%. QTc must be < 450 ms in males and < 470 ms in females.
  • Time from last anti-tumor treatment to first radiation treatment at least 1 week.
  • Recovery from previous cancer treatment (≤ Grade 1 by CTCAE 4.0 criteria) prior to first radiation treatment
  • Women of childbearing potential and males with partners of childbearing potential must agree to the use of barrier methods of contraception, hormonal contraceptives, or to abstain from heterosexual activity for the duration of study participation.
  • Ability to understand and provide voluntary written informed consent

Who cannot join

  • Pregnant or breast feeding. The agents used in this study have the potential to harm a fetus. Radiation is a known teratogen. There is insufficient information regarding potential for fetal harm during immunotherapy at this time. Biological females of childbearing potential must have a negative serum pregnancy test within 14 days of registration.
  • Diagnosis of immunodeficiency
  • Concurrent use of high dose steroids; chronic steroid use of < 2 mg dexamethasone or equivalent per day is permissible
  • Concurrent malignancy requiring active treatment, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ
  • Prior organ allograft or allogeneic transplantation
  • Autoimmune disease
  • Uncontrolled intercurrent or psychiatric illness or social situation that would limit compliance with study requirements
  • Live vaccines within 30 days prior to the first dose of IL-2 and while participating in the trial. Examples of live vaccines include, but are not limited to, measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (eg, Flu - Mist®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center - University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Phase 1b/2 Study of Hypofractionated Radiation and Combination Immunotherapy for Relapsed/Refractory Metastatic Melanoma

This is a Phase 1b/2 study designed to evaluate combination of the human T-cell cytokine Interleukin-2 (IL-2) and a checkpoint inhibitor Ipilimumab immediately following a course of hypofractionated palliative radiation therapy in the management of unresectable, relapsed/refractory metastatic melanoma.

Read the detailed description

The sequential administration of Interleukin-2 (IL-2) following radiation therapy offers a rational immunologic priming strategy to expand antigen primed T cells under the growth promoting effects of Interleukin-2 therapy.

This clinical trial is designed to evaluate the combination of the T cell cytokine Interleukin-2 and the checkpoint inhibitor Ipilimumab in sequential combination following a course of hypofractionated palliative radiation therapy. The addition of single dose Ipilimumab offers rational timing of CTLA-4 checkpoint blockade to decrease activity of regulatory and suppressor T cell subsets following IL-2 based immunotherapy.

Being tested
Interleukin-2 & Ipilimumab (P-Ib), Interleukin-2 & Ipilimumab (P-II)
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.

  • Interleukin-2 & Ipilimumab (P-Ib)Drug

    Also called IL-2, Yervoy

    Phase Ib:

    • Ipilimumab will be administered in a 3 + 3 dose escalation design.
    • The starting dose will be 0.3 mg/kg administered within 7 days of day 1 cycle 2 ALdesleukin (IL-2).
    • If dose limiting autoimmune toxicities (DLTs) are not observed, the next cohort will receive 1.5 mg/kg.
    • The final cohort will receive 3 mg/kg, in the event that cohort 2 does not exhibit DLTs.
    • In the event of excessive toxicity in cohort 1, then a -1 dose level of 0.1 mg/kg may be evaluated in subsequent cohorts. Cohort sizes will increase to 6 patients if 1 of 3 patients in a cohort experience a DLT.
    • Once the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) is declared, no staggering of enrollment is required for accrual.

  • Interleukin-2 & Ipilimumab (P-II)Drug

    Also called IL-2, Yervoy

    Phase II:

    • Interleukin-2 \& Ipilimumab will be administered at the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D).
Study groups in NCT03297463
Study groupRoleWhat they receive
Phase Ib (Dose Escalation)ExperimentalNot described
Receives: Drug: Interleukin-2 & Ipilimumab (P-Ib)
Phase II (Dose Expansion)ExperimentalNot described
Receives: Drug: Interleukin-2 & Ipilimumab (P-II)

What is being measured

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

  1. Phase 1: Maximum Tolerated Dose (MTD)

    Incidence of Adverse Events

    Measured: Cycle 2 Day 1

  2. Phase 1: Maximum Tolerated Dose (MTD)

    Incidence of Adverse Events

    Measured: Cycle 2 Day 15

  3. Phase 1: Maximum Tolerated Dose (MTD)

    Incidence of Adverse Events

    Measured: 30 days after last IL-2

  4. Phase 2: Objective Response Rate (ORR)

    Disease re-assessment includes physical examination, as well as radiographic response assessment (RECIST v1.1) of non-irradiated target lesions using CT (or PET/CT) and/or at MRI.

    Measured: Day 35

  5. Phase 2: Objective Response Rate (ORR)

    Disease re-assessment includes physical examination, as well as radiographic response assessment (RECIST v1.1) of non-irradiated target lesions using CT (or PET/CT) and/or at MRI.

    Measured: 30 days after last IL-2

Secondary outcomes (2)

  1. Progression-free survival (PFS)

    Incidence of PFS

    Measured: Every 3 Months until 2 Years from 1st IL-2 Dose

  2. Overall survival (OS)

    Incidence of OS

    Measured: Every 3 Months until 2 Years from 1st IL-2 Dose

Timeline

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

  1. First posted29 Sep 2017
  2. Study start31 Jan 2018
  3. Primary completion1 Feb 2020 (estimated)
  4. Study completion1 Feb 2020 (estimated)

Why it stopped: Replaced by another study.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03297463
Sponsor's protocol ID
2016LS172
Status last verified
Jul 2018
First submitted
26 Sep 2017
Last updated
1 Aug 2018
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Interleukin-2 & Ipilimumab (P-Ib) and Interleukin-2 & Ipilimumab (P-II) in people with Metastatic Melanoma and Pulmonary Metastases, run by Masonic Cancer Center, University of Minnesota 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 20 inclusion and 8 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: withdrawn, as of the sponsor's last update on 1 Aug 2018. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Phase 1: Maximum Tolerated Dose (MTD) (time frame: Cycle 2 Day 1). The study lists 5 primary outcomes in all. 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 NCT03297463.

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 1 Aug 2018.

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