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Metastatic MelanomaPhase 2NCT02158520

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

A Phase 2 study testing Bevacizumab, Ipilimumab and Laboratory Biomarker Analysis in people with Metastatic Melanoma and Mucosal Melanoma, run by Academic and Community Cancer Research United at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Ipilimumab and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
13 sitesUnited States
Study dates
18 Oct 2013to 30 Oct 2019
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Urine dipstick for proteinuria < 2+ (obtained =< 14 days prior to registration/randomization) (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1 g of protein in 24 hours to be eligible)
  • Negative serum pregnancy test done =< 7 days prior to registration/randomization, for women of childbearing potential only
  • Note:
  • Females: adequate contraception must be used by both patient and partner while receiving study drug and for 12 weeks after the last dose of study drug
  • Males: adequate contraception must be used by both patient and partner while receiving study drug; men who have a partner of childbearing age should also avoid fathering a child for 6 months after the last dose of study drug
  • Ability to understand and the willingness to sign a written informed consent document
  • Mayo Rochester patients only: willingness to provide mandatory blood samples for research purposes

Who cannot join

  • 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);
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  • 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
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Myocardial infarction or unstable angina =< 6 months prior to registration/randomization
  • Clinically significant peripheral vascular disease
  • Deep venous thrombosis or pulmonary embolus =< 1 year of registration/randomization
  • Ongoing need for full-dose oral or parenteral anticoagulation
  • Ongoing anti-platelet treatment other than low-dose aspirin (i.e., aspirin 81 mg by mouth daily)
  • Active bleeding or pathological conditions that carry high risk of bleeding (e.g., known esophageal varices, etc.)
  • Serious, non-healing wound (including wounds healing by secondary intention), ulcer or bone fracture
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 6 months prior to registration/randomization
  • History of central nervous system (CNS) disease (e.g., vascular abnormalities, etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6 months prior to registration/randomization, seizures not controlled with standard medical therapy
  • Radiographically documented tumor invading major blood vessels
  • History of hypertensive crisis or hypertensive encephalopathy
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men and women of reproductive potential who are not using effective birth control methods Note: women of childbearing potential must have a negative serum pregnancy test =< 7 days prior to registration/randomization; adequate contraception must be used while receiving study drug and for 12 weeks after the last dose of study drug, by both women and men and by both patient and partner; men who have a partner of childbearing potential should also avoid fathering a child for 6 months after the last dose of study drug
  • Existence of peripheral sensory neuropathy >= grade 2 (from any cause)
  • History of other malignancy =< 5 years with the exception of basal cell or squamous cell carcinoma of the skin, treated with local resection only, or carcinoma in situ (e.g. of the cervix, breast, prostate, etc.)
  • Radiation therapy (other than palliative) =< 2 weeks prior to randomization; note: patients who have had > 25% of their functional bone marrow irradiated are not eligible for this trial
  • Active or recent history of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) =< 30 days prior to registration/randomization
  • Known hypersensitivity to any of the components of ipilimumab, bevacizumab, or nab-paclitaxel
  • History of inflammatory bowel disease (e.g., Crohn?s, ulcerative colitis) - note patients with irritable bowel syndrome are eligible
  • Diagnosis of autoimmune disease (i.e., rheumatoid arthritis, scleroderma, systemic lupus erythematosus [SLE], autoimmune vasculitis, Guillain-Barre syndrome, etc.), regardless if patient is currently receiving treatment at time of registration/randomization
  • Systemic corticosteroids use =< 2 weeks, regardless of indication; note: patients who are on inhaled corticosteroids are eligible

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Illinois

    Chicago, Illinois, 60612

  • Cancer Research Consortium of West Michigan NCORP

    Grand Rapids, Michigan, 49503

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Saint Mary's Medical Center

    San Francisco, California, 94117

  • Siouxland Regional Cancer Center

    Sioux City, Iowa, 51101

Other trials in United States

About this study

Official title: Randomized Phase II Study of AB (Nab-Paclitaxel [Abraxane?], Bevacizumab) Versus Ipilimumab for Therapy of Unresectable Stage IV Metastatic Malignant Melanoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess whether the combination nab-paclitaxel and bevacizumab (AB) prolongs progression-free status relative to ipilimumab as a treatment in patients with unresectable stage IV melanoma.

SECONDARY OBJECTIVES:

  1. To estimate the hazard of death among those randomized to AB then ipilimumab relative to those randomized to ipilimumab then AB as treatment in patients with unresectable stage IV melanoma.

II. To assess whether tumor response rate (as determined by Response Evaluation Criteria in Solid Tumors [RECIST] criteria 1.1) differs with respect to first (1st) treatment course.

III. To estimate whether the tumor response rate differs with respect to second (2nd) treatment course for those who progressed during their first treatment course.

IV. To further examine the safety profile of each of these regimens.

CORRELATIVE OBJECTIVES:

  1. To examine the pharmacokinetics of nab-paclitaxel when combined with bevacizumab therapy.

II. To examine pharmacodynamic changes of blood-derived parameters (biomarkers) of angiogenesis and immunity as a function of therapy.

III. To examine whether changes in serum biomarkers are also seen in the tumor.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive bevacizumab intravenously (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.

ARM B: 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.

After completion of study treatment, patients are followed up for up to 5 years.

Being tested
Bevacizumab, Ipilimumab, Laboratory Biomarker Analysis, Nab-paclitaxel, Pharmacological Study
Medical subject headings
Melanoma, Uveal Melanoma

What participants receive

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

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02158520
Study groupRoleWhat they receive
Arm A (bevacizumab and nab-paclitaxel)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Other: Laboratory Biomarker Analysis; Drug: Nab-paclitaxel; Other: Pharmacological Study
Arm B (ipilimumab)ExperimentalPatients 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.
Receives: Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

  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.

    Measured: 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)

  1. Overall Survival (OS)

    Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

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

  2. Number of Patients With Tumor Response

    Tumor response defined as complete or partial response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR): Disappearance of all evidence of disease, Partial response (PR): Regression of measurable disease and no new sites.

    Measured: Up to 4 years

  3. The Number of Patients Who Experienced Toxicity

    The number of patients who experienced toxicity (grade 3 or higher adverse events considered at least possibly related to treatment) are reported below.

    Measured: Up to 4 years

Timeline

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

  1. First posted9 Jun 2014 (estimated)
  2. Study start18 Oct 2013
  3. Primary completion24 May 2017
  4. Study completion30 Oct 2019

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02158520
Sponsor's protocol ID
ACCRU RU261206I
Other IDs
NCI-2013-01112, ML28605, RU261206I, ACCRU RU261206I, P30CA015083
Status last verified
Feb 2019
First submitted
5 Jun 2014
Last updated
21 Jan 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Ipilimumab and Laboratory Biomarker Analysis in people with Metastatic Melanoma and Mucosal Melanoma, run by Academic and Community Cancer Research United at 13 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 22 inclusion and 40 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: finished, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 2 Jan 2020). 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?

Progression-free Survival (PFS) (time frame: 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). 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 NCT02158520.

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 21 Jan 2020.

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