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Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

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ClinicalTrials.gov Identifier: NCT02020707
Recruitment Status : Recruiting
First Posted : December 25, 2013
Last Update Posted : August 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This phase I trial studies the side effects and best dose of paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab in treating patients with stage IV melanoma that cannot be removed by surgery or with cancer of the cervix, endometrium, ovary, fallopian tube or peritoneal cavity. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, 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. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. Giving paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab may kill more tumor cells.

Condition or disease Intervention/treatment Phase
Cervical Adenosarcoma Cervical Adenosquamous Carcinoma Cervical Carcinosarcoma Cervical Squamous Cell Carcinoma, Not Otherwise Specified Endometrial Clear Cell Adenocarcinoma Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Adenocarcinoma Endometrial Mucinous Adenocarcinoma Endometrial Squamous Cell Carcinoma Endometrial Transitional Cell Carcinoma Endometrial Undifferentiated Carcinoma Fallopian Tube Adenocarcinoma Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Malignant Ovarian Epithelial Tumor Malignant Peritoneal Neoplasm Ovarian Carcinosarcoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Adenocarcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Primary Peritoneal Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Melanoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Stage IV Skin Melanoma Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma Uterine Corpus Carcinosarcoma Biological: Bevacizumab Other: Laboratory Biomarker Analysis Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation Other: Pharmacological Study Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD-malignant melanoma [MM]) of Abraxane (paclitaxel albumin-stabilized nanoparticle formulation)/bevacizumab-complex (AB-complex) among patients with metastatic malignant melanoma.

II. To determine the maximally tolerated dose (MTD-gynecologic [GYN]) of AB-complex among patients with gynecologic cancers.

SECONDARY OBJECTIVES:

I. To gather preliminary data on tumor response rate and progression free survival time of AB-complex among patients with metastatic malignant melanoma.

II. To gather preliminary data on tumor response rate and progression free survival time of AB-complex among patients with gynecologic cancers.

TERTIARY OBJECTIVES:

I. Pharmacokinetics of paclitaxel administered in the context of AB-complex. II. Tumor concentrations of paclitaxel 24 hour (h) following AB-complex infusion and correlation with plasma levels.

OUTLINE: This is a dose-escalation study.

Patients receive paclitaxel albumin-stabilized nanoparticle formulation/bevacizumab-complex intravenously (IV) over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 12 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Targeted Complex Therapy for Advanced Melanoma and Gynecologic Cancers: Nab-Paclitaxel (Abraxane)/Bevacizumab Complex (AB-Complex)
Actual Study Start Date : February 3, 2014
Estimated Primary Completion Date : February 3, 2020
Estimated Study Completion Date : June 1, 2025


Arm Intervention/treatment
Experimental: Treatment (AB-complex)
Patients receive paclitaxel albumin-stabilized nanoparticle formulation/bevacizumab-complex IV over 30-60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Bevacizumab
Given IV
Other Names:
  • Anti-VEGF
  • Anti-VEGF Humanized Monoclonal Antibody
  • Anti-VEGF rhuMAb
  • Avastin
  • Bevacizumab Biosimilar BEVZ92
  • Bevacizumab Biosimilar BI 695502
  • Bevacizumab Biosimilar FKB238
  • 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

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation
Given IV
Other Names:
  • ABI 007
  • ABI-007
  • Abraxane
  • Albumin-bound Paclitaxel
  • Albumin-Stabilized Nanoparticle Paclitaxel
  • nab-paclitaxel
  • Nanoparticle Albumin-bound Paclitaxel
  • Nanoparticle Paclitaxel
  • protein-bound paclitaxel

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. MTD of AB-complex, defined as the highest dose level among those under consideration where at most 1 of 6 patients develops a dose-limiting toxicity [ Time Frame: 28 days ]
    The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Time from study entry to death due to any cause, assessed up to 12 months ]
  2. Progression-free survival (PFS) [ Time Frame: Time from study entry to the documentation of disease progression, assessed up to 12 months ]
  3. Tumor response, defined as complete response or partial response on 2 consecutive evaluations at least 8 weeks apart assessed by Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Melanoma cohort only: histologic proof of surgically unresectable stage IV malignant melanoma
  • Melanoma cohort only: measurable disease defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with computed tomography (CT) scan or magnetic resonance imaging (MRI) scan; or CT component of a positron emission tomography (PET)/CT; NOTE: disease that is measurable by physical examination only is not eligible
  • Gynecologic cancer cohort only: histologic proof of epithelial cervical, endometrial, ovarian, fallopian, or primary peritoneal cancers; allowable histologies for cervical cancer include squamous cell carcinoma, adenocarcinoma, and mixed/adenosquamous carcinoma; allowable histologies for endometrial cancer include endometrioid, serous, clear cell, mucinous, squamous, transitional cell, undifferentiated, mixed, and carcinosarcoma (this is considered a poorly differentiated epithelial tumor); allowable histologies for ovarian, fallopian, and peritoneal cancer include serous, clear cell, endometrioid, mucinous, transitional cell, undifferentiated, mixed, and carcinosarcoma
  • For ovarian, fallopian tube, and peritoneal cancers only: platinum-resistant, defined as =< 183 days from the date of the most recent dose of chemotherapy containing either carboplatin or cisplatin until the first evidence of cancer recurrence or progression either symptoms directly attributable to cancer, radiographic recurrence of cancer, or cancer antigen 125 (CA-125) > 70, confirmed >= 7 days later (confirmation of elevated CA-125 may be beyond 183 days and still count as platinum-resistant)
  • Gynecologic cancer cohort only: measureable disease, defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with CT scan or MRI scan; or CT component of a PET/CT; NOTE: Disease that is measurable by physical examination only is not eligible; EXCEPTION: Patients with ovarian, fallopian, or peritoneal cancer without measurable disease are eligible if two pretreatment CA125 values (documented on two occasions taken at least one week apart) are at least twice the upper limit of normal or twice the nadir value if pretreatment CA125 values never normalized.
  • At least one prior systematic therapy in the metastatic setting
  • Hemoglobin >= 9.0 g/dL (patients may be transfused to meet hemoglobin [Hgb] requirement)
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count (PLT) >= 100,000/mm^3
  • Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 0.4 mg/dL
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x upper limit of normal (ULN)
  • Creatinine =< 1.5 x ULN
  • Absence of proteinuria at screening as demonstrated by one of the following:

    • Urine protein/creatinine (UPC) ratio < 1.0 at screening OR
    • Urine dipstick for proteinuria < 2+ (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)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Sensory peripheral neuropathy =< grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 4.0)
  • Motor peripheral neuropathy = grade 0 (per CTCAE v. 4.0)
  • Ability to understand and the willingness to sign a written informed consent document
  • Willing to return to enrolling institution for follow-up 2-4 weeks after treatment discontinuation
  • Life expectancy >= 90 days (3 months)
  • Willing to provide blood samples for correlative research purposes
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy; EXCEPTION: For platinum-resistant ovarian cancer, because nab-paclitaxel has known benefit, patients who may benefit from standard single agent chemotherapy are also eligible to participate
  • Prior therapy with an angiogenesis inhibitor
  • Any anti-cancer therapy or investigational agents =< 4 weeks prior to registration
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • Brain metastases per MRI or CT at any time prior to registration; NOTE: patients that have had primary therapy for brain metastasis (i.e. surgical resection, whole brain radiation, or stereotactic radiotherapy [SRT] even if stable) are not eligible
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Other active malignancy =< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • 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
    • Immuno-compromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
    • 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
    • Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
    • Clinically significant peripheral vascular disease
    • History of central nervous system (CNS) disease (e.g., primary brain tumor, vascular abnormalities, etc.), clinically significant stroke or transient ischemic attack (TIA) =< 6 months prior to registration, seizures not controlled with standard medical therapy
    • History of hypertensive crisis or hypertensive encephalopathy
    • Therapeutic anticoagulation requiring international normalized ratio (INR) > 2.0
  • For gynecologic cancer cohort only recurrent or progressive disease within 30 days of the last dose of weekly paclitaxel or nab-paclitaxel
  • History of inflammatory bowel disease requiring ongoing therapy
  • History of diverticulitis or pancreatitis within 12 weeks of registration
  • History of grade 3 or 4 bowel toxicity from immune checkpoint inhibitor within 12 weeks of registration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02020707


Locations
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United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Svetomir N. Markovic         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Svetomir Markovic Mayo Clinic

Additional Information:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02020707     History of Changes
Other Study ID Numbers: MC1371
NCI-2013-01782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1371 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: December 25, 2013    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: March 2019
Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Transitional Cell
Fallopian Tube Neoplasms
Cystadenocarcinoma, Serous
Carcinoma, Endometrioid
Carcinosarcoma
Mixed Tumor, Mullerian
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Adenocarcinoma, Clear Cell
Peritoneal Neoplasms
Carcinoma, Adenosquamous
Adenosarcoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases