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Metastatic MelanomaPhase 2NCT02748564

Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

A Phase 2 study testing Aldesleukin, Laboratory Biomarker Analysis and Pembrolizumab in people with Metastatic Melanoma and Stage III Mucosal Melanoma of the Head and Neck, run by Rutgers, The State University of New Jersey at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study will evaluate the safety and tolerability of IL-2 when given in combination with pembrolizumab to patients with advanced melanoma. Aldesleukin may stimulate white blood cells to melanoma cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Aldesleukin, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
5 sitesUnited States
Study dates
21 Mar 2017to 5 Jun 2023
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 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Histologic or cytologic diagnosis of cutaneous melanoma, mucosal melanoma, or melanoma of unknown primary that is considered unresectable (stage III) or metastatic (stage IV)
  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease evident on radiographs (preferred) or clinical examination; for this protocol, measurable disease is defined as at least one evaluable tumor that is at least 10 mm in longest dimension
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Patients must have a brain magnetic resonance imaging (MRI) or computed tomography (CT) (with and without contrast) that is free of active metastases; metastases that have been treated with radiation or surgical resection, are stable for at least 4 weeks and do not require steroids are eligible
  • Normal cardiac function; patients who have a history of heart disease, or who are over the age of 50 years must have a normal cardiac stress test within the prior 90 days
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  • Normal lung function; patients who have extensive pulmonary metastases or any chronic pulmonary disease history must have pulmonary function testing demonstrating forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) > 65% of predicted values
  • Absolute neutrophil count (ANC) >= 1,500 /mcL
  • Platelets >= 100,000 / mcL
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential should 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 should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the 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
  • Male subjects should 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
  • Subject meets institutional requirements for IL-2 therapy

Who cannot join

  • Has primary ocular melanoma
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic immunosuppressive steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment; exception: physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is not considered systemic immunosuppressive steroid therapy
  • Has received previous high dose IL-2 therapy, any programmed death (PD)-1 blocking antibody (e.g. pembrolizumab, nivolumab), or any programmed death ligand (PD-L)1 blocking antibody in the metastatic setting; prior therapy with any PD-1 blocking antibody is allowed if given in the adjuvant setting and the last dose was > 6 months prior to study entry; prior therapy with ipilimumab is allowed (in the adjuvant or metastatic setting); other prior therapy (in the adjuvant or the metastatic setting) is allowed, including targeted therapy, chemotherapy, or experimental therapy
  • Has a history of significant congestive heart failure or significant pulmonary disease
  • Has a known history of active TB (bacillus tuberculosis)
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  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 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 and/or alopecia are exceptions to this criterion and may qualify for the study
  • Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Indiana University

    Bloomington, Indiana, 46996

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • Cardinal Bernardin Cancer Center

    Maywood, Illinois, 60153

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

Other trials in United States

About this study

Official title: Trial of Interleukin-2 in Combination With Pembrolizumab for Patients With Unresectable or Metastatic Melanoma

This study will evaluate the safety and tolerability of IL-2 when given in combination with pembrolizumab to patients with advanced melanoma. Aldesleukin may stimulate white blood cells to melanoma cells. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving aldesleukin and pembrolizumab may kill more tumor cells.

There are two parts to this study:

  • Phase Ib: To determine the safety and side effects of increasing doses of IL-2 in combination with pembrolizumab
  • Phase II: Once the maximum tolerated dose of IL-2 is determined, additional patients will be treated to determine if it is effective against the cancer.
Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine an optimal tolerated dose (OTD) of aldesleukin (interleukin [IL]-2) that is effective and tolerable in combination with pembrolizumab.

II. To characterize the efficacy of the OTD of IL-2 in combination with pembrolizumab.

SECONDARY OBJECTIVES:

  1. To characterize the safety of IL-2 in doses ranging up to the Food and Drug Administration (FDA)- approved dose when administered in combination with pembrolizumab.

II. To characterize clinical endpoints, including overall survival, progression-free survival, and complete response rate.

TERTIARY OBJECTIVES:

  1. To characterize immune parameters in the blood and tumor microenvironment and cellular and molecular features of the tumor tissue that correlate with response to combination therapy for study as potential predictive biomarkers.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 every 3 weeks and aldesleukin IV every 8 hours for up to 14 doses at weeks 4, 7, 16, 19, 28, and 31 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months up to 10 years.

Being tested
Aldesleukin, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Melanoma

What participants receive

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

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02748564
Study groupRoleWhat they receive
Treatment (pembrolizumab, aldesleukin)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 every 3 weeks and aldesleukin IV every 8 hours for up to 14 doses at weeks 4, 7, 16, 19, 28, and 31 in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Best Overall Response Rate as Assessed by Response (BORR) Evaluation Criteria in Solid Tumors Version 1.1, With the Modification That Progressive Disease Must be Confirmed on a Subsequent Scan

    Estimated using OTD of IL-2 and pembrolizumab assessed by Response Evaluation Criteria in Solid Tumors version 1.1,for target lesions and assessed by CT or MRI imaging: Complete response (CR) - disappearance of all target lesions; Partial response (PR) - >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) - At least a 20% increase in the sum of the longest diameter of target lesions; or Stable Disease (SD) - neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    By testing increasing doses up to 600,000 IU. Receive IL-2 6,000 International Units per kilogram (IU/kg);in cycles 2, 3, 6,7,10 and 11, with follow up thirty days after the last dose of study drug

    Measured: Four to six weeks later up to one year

Secondary outcomes (4)

  1. Complete Response Rate

    Participants are treated with pembrolizumab and the MTD of IL-2. Will be measured using the RECIST v 1.1. For all participants who experience a complete response, the date noted for disease response is the time of the scan when it was originally determined, and not the later date of the confirmatory scan.

    Measured: Four to six weeks later, up to three years

  2. Number of Adverse Effects (AE) as Evaluated by National Cancer Institute Common Terminology Criteria for AE's, Version 4.0

    Each participant will be assessed for potential or new worsening AE's. AE's will be graded and recorded through the study and during follow-up period according to National Cancer Institute Common Terminology Criteria for AE's, version 4.0. Grade 1-5 with grade 5 being the most severe.

    Measured: Thirty days after last dose of treatment, up to three years

  3. Overall Survival Estimated Using Kaplan-Meier Curves

    Assess for survival status until death. Time to death measured in months.

    Measured: Baseline to end of follow-up, up to 3 years

  4. Progressive Free Survival Retaining Progression-free Survival Status up to 36 Months

    As measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for targeted lesions; Partial response (PR) - >= 30% increase in the sum of the longest diameter of target lesions; or stable (SD) - neither sufficient shrinkage to quality for PR nor Sufficient increase to quality PD. Descriptive statistical will be used. Continuous variables will be presented by summary statistics (such as mean, median, standard error and 90% CI) and the categorical variables by frequency distributions (i.e., frequency counts, percentages and 90% CI).

    Measured: Up to three years

Timeline

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

  1. First posted22 Apr 2016 (estimated)
  2. Study start21 Mar 2017
  3. Primary completion18 Oct 2018
  4. Study completion5 Jun 2023

Why it stopped: Study Complete

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
Sequential
Model description
Dose escalation study
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02748564
Sponsor's protocol ID
091602
Other IDs
NCI-2016-00466, Pro20160000394, P30CA072720
Status last verified
Aug 2023
First submitted
19 Apr 2016
Last updated
3 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Silk AW, Curti B, Bryan J, Saunders T, Shih W, Kane MP, Hannon P, Fountain C, Felcher J, Zloza A, Kaufman HL, Mehnert JM, McDermott DF. A phase Ib study of interleukin-2 plus pembrolizumab for patients with advanced melanoma. Front Oncol. 2023 Feb 9;13:1108341. doi: 10.3389/fonc.2023.1108341. eCollection 2023.

    PubMed 36845705

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aldesleukin, Laboratory Biomarker Analysis and Pembrolizumab in people with Metastatic Melanoma and Stage III Mucosal Melanoma of the Head and Neck, run by Rutgers, The State University of New Jersey at 5 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 20 inclusion and 23 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: stopped early, as of the sponsor's last update on 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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?

Yes. Results are posted in the registry (first posted 9 Feb 2023). 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?

Best Overall Response Rate as Assessed by Response (BORR) Evaluation Criteria in Solid Tumors Version 1.1, With the Modification That Progressive Disease Must be Confirmed on a Subsequent Scan (time frame: Four to six weeks later up to one year). 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 NCT02748564, which also lists 1 linked publication.

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 3 Aug 2023.

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