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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

NCT02020707

Description:

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.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Melanoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers
  • Official Title: Targeted Complex Therapy for Advanced Melanoma and Gynecologic Cancers: Nab-Paclitaxel (Abraxane)/Bevacizumab Complex (AB-Complex)

Clinical Trial IDs

  • ORG STUDY ID: MC1371
  • SECONDARY ID: NCI-2013-01782
  • SECONDARY ID: MC1371
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02020707

Conditions

  • 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

Interventions

DrugSynonymsArms
BevacizumabAnti-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-VEGFTreatment (AB-complex)
Paclitaxel Albumin-Stabilized Nanoparticle FormulationABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, nab-paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, protein-bound paclitaxelTreatment (AB-complex)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (AB-complex)ExperimentalPatients 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.
  • Bevacizumab
  • Paclitaxel Albumin-Stabilized Nanoparticle Formulation

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Overall survival (OS)
Time Frame:Time from study entry to death due to any cause, assessed up to 12 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Time from study entry to the documentation of disease progression, assessed up to 12 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

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