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

NCT02748564 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: 091602NCI-2016-00466Pro20160000394P30CA072720
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

Outcome Measures

Primary Outcomes (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

  Four to six weeks later up to one year

Secondary Outcomes (4)

• Complete Response Rate

  Four to six weeks later, up to three years

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

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

• Overall Survival Estimated Using Kaplan-Meier Curves

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

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

  Up to three years

Study Arms (1)

Treatment (pembrolizumab, aldesleukin)

EXPERIMENTAL

Patients 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.

Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Aldesleukin BIOLOGICAL

Given IV

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (pembrolizumab, aldesleukin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, aldesleukin)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, aldesleukin)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Indiana University

Bloomington, Indiana, 46996, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203, United States

Location

Related Publications (1)

• 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.

  PMID: 36845705 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Adam Berger, MD
• Organization: Cancer Institute of New Jersey

ab2047@cinj.rutgers.edu

215-235-8079

Study Officials

• Adam Berger, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine Medical Oncology

Model Details: Dose escalation study

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: April 22, 2016
• Study Start: March 21, 2017
• Primary Completion: October 18, 2018
• Study Completion: June 5, 2023
• Last Updated: August 3, 2023
• Results First Posted: February 9, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)