Aldesleukin With or Without Ziv-Aflibercept in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

NCT01258855 | Completed Phase 2 Results

• 11 other identifiers: NCI-2011-02498PHII-107CHNMC-PHII-107CDR00006906548628N01CM00038N01CM00070N01CM00071N01CM62209P30CA033572UM1CA186705
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 21

Brief Summary

This randomized phase II trial studies how well aldesleukin with or without ziv-aflibercept works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Aldesleukin may stimulate the white blood cells to kill cancer. Ziv-aflibercept may stop the growth of melanoma by blocking blood flow to the tumor. It is not yet known whether aldesleukin is more effective with or without ziv-aflibercept in treating melanoma.

Conditions

Metastatic Melanoma; Recurrent Melanoma; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  The time from the date of randomization until date of progression, death, or recurrence, assessed up to 5 years

Secondary Outcomes (5)

• Overall Survival

  Until Death from any cause, up to 5 years

• Response Rate

  Up to 5 years

• Count of Participants With Adverse Events

  Up to 5 years

• Progression-free Survival for Patients With High Vascular Endothelial Growth Factor (VEGF) Levels

  Up to 5 years

• Progression-free Survival for Patients With Low VEGF Levels

  Up to 5 years

Other Outcomes (1)

• 1-year Overall Survival Rate

  Until Death from any cause, up to 1 year

Study Arms (2)

Arm I (ziv-aflibercept and aldesleukin)

EXPERIMENTAL

Patients receive ziv-aflibercept IV over at least 1 hour in weeks 1, 3, 5, and 7 (and in week 9 of course 1 only) and high-dose aldesleukin IV over 15 minutes every 8 hours for 5 days in weeks 1 and 3 (and in weeks 3 and 5 of course 1 only). Treatment repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising ziv-aflibercept IV on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: Ziv-Aflibercept

Arm II (aldesleukin)

EXPERIMENTAL

Patients receive high-dose aldesleukin IV over 15 minutes every 8 hours for 5 days in weeks 1 and 3. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Biological: Aldesleukin; Other: Laboratory Biomarker Analysis

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

Arm I (ziv-aflibercept and aldesleukin); Arm II (aldesleukin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (ziv-aflibercept and aldesleukin); Arm II (aldesleukin)

Ziv-Aflibercept BIOLOGICAL

Given IV

Also known as: AFLIBERCEPT, AVE0005, Eylea, vascular endothelial growth factor trap, VEGF Trap, VEGF Trap R1R2, VEGF-Trap, Zaltrap

Arm I (ziv-aflibercept and aldesleukin)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic melanoma (includes American Joint Committee on Cancer \[AJCC\] stage IV or advanced/inoperable stage III; also includes patients with a history of lower stage melanoma and subsequent recurrent metastatic disease that is either locally/regionally advanced/inoperable disease or distant metastases)
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 10 mm with computed tomography (CT) scan or clinically (must be measurable with calipers) according to RECIST version 1.1
• Patients must be free of brain metastasis by contrast-enhanced CT/magnetic resonance imaging (MRI) scans within 4 weeks prior to enrollment; if known to have prior brain metastases, must not have evidence of active brain disease after definitive therapy (surgery, radiation therapy, or stereotactic radiosurgery) on two successive MRI evaluations at least 3 months apart (one of which is =\< 4 weeks prior to starting the study drugs)
• A patient may be treatment naïve; however, up to two prior regimens for metastatic melanoma are allowed; prior adjuvant interferon (IFN)-alpha is allowed; no prior therapy with bevacizumab, aflibercept or interleukin-2 (IL-2)
• Patients must not have received systemic therapy or radiotherapy within the preceding 4 weeks; patients must have recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery, and be free of significant detectable infection
• For patients who have received prior anti-cytotoxic T-lymphocyte antigen (CTLA)4 monoclonal antibody therapy (ipilimumab or tremelimumab), there is a risk of bowel perforation with IL-2 therapy; therefore, for these patients if they have a history of colitis or diarrhea during anti-CTLA4 monoclonal antibody therapy, they should have a formal evaluation by a gastroenterologist and a colonoscopy should be considered to demonstrate the absence of active bowel inflammation before initiating IL-2 therapy on this protocol
• Life expectancy of greater than 3 months in the opinion of the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky \> 70%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Total bilirubin within 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine within 1.5 x institutional upper limit of normal OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine level above institutional normal

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with brain metastases should be excluded from this clinical trial except as noted above
• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, and patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study
• Serious or non-healing wound, ulcer, or bone fracture
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
• Patients with the following invasive procedures:
• Major surgical procedures, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy
• Anticipation of need for major surgical procedures during the course of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1 of therapy; central venous catheter placements are permitted to be completed 7 or more days prior to day 1 of therapy; however, peripherally inserted central catheter (peripherally inserted central catheter \[PICC\] or PIC line) may be placed at any time prior to or during therapy
• Patients with clinically significant cardiovascular or cerebrovascular disease:
• History of cerebrovascular accident or transient ischemic attack within past 6 months
• Uncontrolled hypertension, defined as blood pressure \> 150/100 mm Hg or systolic blood pressure (BP) \> 180 mm Hg if diastolic blood pressure \< 90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months
• Myocardial infarction, coronary artery bypass graft (CABG) or unstable angina within the past 6 Months
• New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (21)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

City of Hope South Pasadena

South Pasadena, California, 91030, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; aflibercept

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: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-218-5265

Study Officials

• Ahmad Tarhini

  City of Hope Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: January 18, 2011
• Primary Completion: March 29, 2018
• Study Completion: March 29, 2018
• Last Updated: May 10, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-05

Locations

US (21)