Nab-Paclitaxel and Bevacizumab or Ipilimumab as First-Line Therapy in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery

NCT02158520 | Completed Phase 2 Results DMC

• 5 other identifiers: ACCRU RU261206INCI-2013-01112ML28605RU261206IP30CA015083
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 13

Brief Summary

This randomized phase II trial studies how well nab-paclitaxel and bevacizumab or ipilimumab works as first-line therapy in treating patients with stage IV melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may stop the growth of tumor cells by binding to a protein called vascular endothelial growth factor (VEGF) and by preventing the growth of new blood vessels that tumors need to grow. Ipilimumab blocks a substance called cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) on the surface of T cells and may help the immune system kill cancer cells. It is not yet known whether nab-paclitaxel and bevacizumab is more effective than ipilimumab in treating melanoma.

Conditions

Metastatic Melanoma; Mucosal Melanoma; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Uveal Melanoma AJCC v7; Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study or a measurable increase in a non-target lesion, or the appearance of new lesions.

  From randomization to the earliest documentation of progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) or death from any cause without the documentation of progression, assessed up to 4 years

Secondary Outcomes (3)

• Overall Survival (OS)

  From registration to death due to any cause, assessed up to 4 years

• Number of Patients With Tumor Response

  Up to 4 years

• The Number of Patients Who Experienced Toxicity

  Up to 4 years

Other Outcomes (3)

• Changes in Biomarkers of Angiogenesis (Arm A)

  Baseline to up to 5 years

• Changes in Biomarkers of Immunity

  Baseline to up to 5 years

• Pharmacokinetic Changes in Paclitaxel Albumin-stabilized Nanoparticle Formulation Plasma Concentrations

  Baseline, prior to the end of paclitaxel albumin-stabilized nanoparticle formulation infusion, and the morning after nab-paclitaxel infusion on days 1 and 8 of course 1

Study Arms (2)

Arm A (bevacizumab and nab-paclitaxel)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm B within 2-4 weeks.

Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Nab-paclitaxel; Other: Pharmacological Study

Arm B (ipilimumab)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may cross-over to Arm A within 2-4 weeks.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Arm A (bevacizumab and nab-paclitaxel)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm B (ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (bevacizumab and nab-paclitaxel); Arm B (ipilimumab)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound Paclitaxel

Arm A (bevacizumab and nab-paclitaxel)

Pharmacological Study OTHER

Correlative studies

Arm A (bevacizumab and nab-paclitaxel); Arm B (ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Histologic or cytologic proof of surgically unresectable stage IV malignant melanoma - including that of uveal and mucosal origin
• Note: biopsy can be of locoregional disease in setting of clinically evident stage IV disease; a biopsy of the primary tumor alone does not fulfill this requirement
• No more than 2 prior courses of systemic therapy for metastatic melanoma
• For patients with metastatic melanoma not of uveal origin, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation determination using a Clinical Laboratory Improvement Amendments (CLIA)-approved testing method on metastatic tumor tissue
• NOTE: patients with metastatic melanoma of uveal origin do not need to have formal BRAF testing due to low probability of a BRAF V600 mutation in their metastatic tumor
• Measurable disease; note: disease that is measurable by physical examination only is not eligible
• Life expectancy of \>= 4 months
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count \>=1500/mL (obtained =\< 14 days prior to registration/randomization)
• Platelet count \>= 100,000 x 10\^9/L (obtained =\< 14 days prior to registration/randomization)
• Hemoglobin \>= 9 g/dL (obtained =\< 14 days prior to registration/randomization) (patients may be transfused to meet this requirement)
• Creatinine =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration/randomization); institutional norms are acceptable
• Total bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to registration/randomization) (exception: patients with documented Gilbert?s syndrome are allowed to participate despite elevated bilirubin)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.5 x ULN and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN (obtained =\< 14 days prior to registration/randomization)
• Alkaline phosphatase =\< 2.5 x ULN (obtained =\< 14 days prior to registration/randomization); if bone metastasis is present in the absence of liver metastasis then =\< 5 x ULN

You may not qualify if:

• Brain metastases per magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: patients who have had therapy for brain metastasis (i.e., surgical resection, whole brain radiation, or stereotactic radiosurgery \[SRS\] even if stable) are not eligible
• Other investigational agents =\< 4 weeks prior to registration/ randomization
• Anti-cancer therapy (including immunotherapy) =\< 4 weeks prior to registration/randomization; exception: adjuvant Leukine =\< 14 days prior to registration/randomization
• Prior treatment in the adjuvant or metastatic setting with any of the following:
• Agents disrupting VEGF activity or targeting vascular endothelial growth factor receptor (VEGFR);
• Ipilimumab;
• Or taxane based chemotherapy regimens (including paclitaxel, docetaxel, cabazitaxel or nab-paclitaxel)
• Major surgical procedure, open biopsy, or significant traumatic injury =\< 4 weeks prior to registration/randomization; (port-a-cath placement does not count as a major surgical procedure and patients can be enrolled at any time after placement)
• Fine needle aspirations or core biopsies =\< 7 days prior to registration/ randomization
• Planned/or anticipated major surgical procedure during the course of the study
• Other medical conditions including but not limited to:
• History of liver disease such as cirrhosis, chronic active hepatitis, chronic persistent hepatitis or hepatitis B or C
• Active infection requiring parenteral antibiotics
• Poorly controlled high blood pressure (\>= 150 mmHg systolic and/or 100 mmHg diastolic) despite treatment

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (13)

Saint Mary's Medical Center

San Francisco, California, 94117, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Siouxland Regional Cancer Center

Sioux City, Iowa, 51101, United States

Location

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Ipilimumab; CTLA-4 Antigen; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes

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; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Svetomir N. Markovic MD, PhD
• Organization: Mayo Clinic

markovic.svetomir@mayo.edu

507/266-0800

Study Officials

• Svetomir N Markovic

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: June 5, 2014
• First Posted: June 9, 2014
• Study Start: October 18, 2013
• Primary Completion: May 24, 2017
• Study Completion: October 30, 2019
• Last Updated: January 21, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-02

Locations

US (13)