Nab-Paclitaxel and Bevacizumab in Treating Patients With Unresectable Stage IV Melanoma or Gynecological Cancers

  • STATUS
    Recruiting
  • End date
    Jun 1, 2025
  • participants needed
    73
  • sponsor
    Mayo Clinic
Updated on 4 May 2022
ct scan
platelet count
metastatic melanoma
paclitaxel
cancer
absolute neutrophil count
monoclonal antibodies
chest x-ray
measurable disease
carcinoma
tumor growth
direct bilirubin
squamous cell carcinoma
x-rays
MRI
cavity
neutrophil count
tumor cells
monoclonal antibody therapy
bevacizumab
biomarker analysis
positron emission tomography
neuropathy
adenocarcinoma
fallopian tube
pet/ct scan
cervical carcinoma
protein/creatinine
cancer antigen 125
peritoneal cancer
carcinoma of cervix

Summary

This phase I trial studies the side effects and best dose of nab-paclitaxel and bevacizumab in treating patients with stage IV melanoma that cannot be removed by surgery (unresectable), cancer of the cervix, endometrium, ovary, fallopian tube or peritoneal cavity. 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 or slow tumor growth by blocking the growth of new blood vessels necessary for tumor growth. Giving nab paclitaxel and bevacizumab may kill more tumor cells than nab-paclitaxel alone.

Description

PRIMARY OBJECTIVES:

I. To determine the maximally tolerated dose (MTD-malignant melanoma [MM]) of Abraxane (nab-paclitaxel)/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.

III. To further assess the safety profile and anti-tumor activity of the recommended phase II dose of AB-complex for patients with previously-treated endometrial cancer IV. To further assess the safety profile and anti-tumor activity of the recommended phase II dose of AB-complex for patients with previously treated ovarian cancer

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.

CORRELATIVE OBJECTIVES (DOSE-ESCALATION COHORTS ONLY):

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 nab-paclitaxel/bevacizumab-complex intravenously (IV) over 30-60 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may receive paclitaxel if supply of nab-paclitaxel is exhausted.

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

Details
Condition Cervical Adenocarcinoma, Cervical Adenosarcoma, Cervical Adenosquamous Carcinoma, Cervical Carcinosarcoma, Cervical Squamous Cell Carcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Mixed Cell Adenocarcinoma, Endometrial Mucinous Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Undifferentiated Carcinoma, Fallopian Tube Adenocarcinoma, Fallopian Tube Carcinosarcoma, Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Mucinous Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma, Fallopian Tube Squamous Cell Carcinoma, Fallopian Tube Transitional Cell Carcinoma, Fallopian Tube Undifferentiated Carcinoma, Malignant Female Reproductive System Neoplasm, Malignant Ovarian Clear Cell Tumor, Malignant Ovarian Endometrioid Tumor, Malignant Ovarian Epithelial Tumor, Malignant Ovarian Mucinous Tumor, Malignant Peritoneal Neoplasm, Malignant Solid Neoplasm, Ovarian Carcinosarcoma, Ovarian Clear Cell Adenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian High Grade Serous Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, Ovarian Serous Adenocarcinoma, Ovarian Transitional Cell Carcinoma, Ovarian Undifferentiated Carcinoma, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Ovarian Carcinoma, Platinum-Resistant Primary Peritoneal Carcinoma, Platinum-Sensitive Ovarian Carcinoma, Primary Peritoneal Carcinosarcoma, Primary Peritoneal Clear Cell Adenocarcinoma, Primary Peritoneal Serous Adenocarcinoma, Primary Peritoneal Transitional Cell Carcinoma, Primary Peritoneal Undifferentiated Carcinoma, Stage IV Cutaneous Melanoma AJCC v6 and v7, Unresectable Melanoma, Uterine Corpus Carcinosarcoma
Treatment laboratory biomarker analysis, bevacizumab, Nab-paclitaxel, pharmacological study, paclitaxel albumin-stabilized nanoparticle formulation
Clinical Study IdentifierNCT02020707
SponsorMayo Clinic
Last Modified on4 May 2022

Eligibility

Yes No Not Sure

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 cohorts only (dose escalation and dose expansion cohorts)
Dose escalation 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
Endometrial cancer expansion cohort only
At least one prior systematic therapy in the metastatic setting
Histologic proof of endometrial cancer including endometrioid, serous, clear cell, mucinous, undifferentiated, mixed, and carcinosarcoma histologies
-3 lines of cytotoxic or immune checkpoint inhibitor therapy (not including hormonal therapy or other regimens not containing cytotoxic agents or immune checkpoint inhibitors)
If one (1) prior line of therapy, must have contained a taxane, a platinum drug, and and immune checkpoint inhibitor
If 2-3 prior lines of therapy, at least one must have contained a taxane and a platinum drug, and at least one must have contained an immune checkpoint inhibitor
Ovarian cancer expansion cohort only
Histologic proof of ovarian cancer including high grade serous, endometrioid, clear cell, mucinous, transitional cell, undifferentiated, mixed, and carcinosarcoma histologies
-4 lines of cytotoxic chemotherapy (not including hormonal therapy or other non-cytotoxic regimens)
At least one prior line of chemotherapy must have contained a taxane and a platinum agent
Urine protein/creatinine (UPC) ratio < 1.0 at screening OR
If 1 or 2 prior lines of chemotherapy, patient's disease must be platinum-resistant
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)
NOTE: Platinum-resistance is defined as any of the following occurring < 183 days after the last dose of platinum-based chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Development of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
Sensory peripheral neuropathy =< grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 4.0)
Progression of radiographic disease (per RECIST 1.1)
Motor peripheral neuropathy = grade 0 (per CTCAE v. 4.0)
Increase in CA-125 level to >= 2 x upper limit of normal (ULN) (if within normal limits [WNL] at the completion of platinum-based chemotherapy)
Ability to understand and the willingness to sign a written informed consent document
If CA-125 is used to determine the date of progression then it must be confirmed by a second CA-125 value >= 7 days after the first level; the date of the first qualifying CA-125 is used to compute the platinum-free interval
Willing to return to enrolling institution for follow-up 2-4 weeks after treatment discontinuation
Increase in CA-125 level to >= 2 x nadir (if nadir > ULN)
Life expectancy >= 90 days (3 months)
If CA-125 is used to determine the date of progression then it must be confirmed by a second CA-125 value >= 7 days after the first level; the date of the first qualifying CA-125 is used to compute the platinum-free interval
Willing to provide blood samples for correlative research purposes
If 3-4 prior lines of chemotherapy, may be platinum-resistant or
platinum-sensitive
At least one prior line of cytotoxic chemotherapy must also have contained
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)
bevacizumab
Prior allergic reaction to carboplatin or cisplatin
Dose escalation cohort: For ovarian, fallopian tube, and peritoneal cancers only: Must
meet criteria for one option below
NOTE: exception for patients with metastatic uveal or mucosal melanoma for which there are no effective/approved front line systemic treatments
Measurable disease, defined as at least one lesion whose longest diameter can be
Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)
accurately measured as >= 2.0 cm with chest x-ray, or as >= 1.0 cm with CT
Platelet count (PLT) >= 100,000/mm^3 (obtained =< 14 days prior to registration)
scan or MRI scan; or CT component of a PET/CT; NOTE: Disease that is
Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 0.4 mg/dL (obtained =< 14 days prior to registration)
measurable by physical examination only is not eligible; EXCEPTION: Patients
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 x ULN (obtained =< 14 days prior to registration)
with ovarian, fallopian, or peritoneal cancer without measurable disease are
Creatinine =< 1.5 x ULN (obtained =< 14 days prior to registration)
eligible if two pretreatment CA125 values (documented on two occasions taken
Alkaline phosphatase =< 2.5 x ULN (obtained =< 14 days prior to registration)
at least one week apart) are at least twice the upper limit of normal or twice
Absence of proteinuria at screening as demonstrated by one of the following (obtained =< 14 days prior to registration)
the nadir value if pretreatment CA125 values never normalized
Hemoglobin >= 9.0 g/dL (patients may be transfused to meet hemoglobin [Hgb]
requirement) (obtained =< 14 days prior to registration)
Negative pregnancy test done =< 7 days prior to registration, for persons 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
Any anti-cancer therapy or investigational agents =< 4 weeks prior to registration
Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
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
History of inflammatory bowel disease requiring ongoing therapy
Prior therapy with an angiogenesis inhibitor =< 28 days prior to registration
No more than 3 systemic therapies (cytotoxic or immunologic) =< 2 years prior to registration
Melanoma cohort only: Treatment with ipilimumab =< 6 months prior to registration
unknown
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic treatment, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (e.g., drug addiction) that would limit compliance with study requirements
History or indication of brain metastases per MRI or CT at any time prior to registration
NOTE: Patients who have had primary therapy for brain metastasis (i.e. surgical resection, whole brain radiation, or SRT even if stable) are not eligible
Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and
newborn are
Conditions that increase the risk of venous thrombosis and/or pulmonary emboli including, but not limited to: prior history of deep venous thrombosis or pulmonary emboli, atrial fibrillation, paroxysmal atrial fibrillation, known and documented thrombophilia requiring long term anticoagulation therapy, permanent intravenous indwelling catheters, severe obesity (body mass index [BMI] > 40)
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
History of diverticulitis or pancreatitis =< 6 months prior to registration
study or interfere significantly with the proper assessment of safety and
History of grade 3 or 4 bowel toxicity from immune checkpoint inhibitor =< 12 weeks prior to registration
toxicity of the prescribed regimens
Invasive surgery =< 6 weeks prior to registration, or planned elective invasive surgery during study treatment
For gynecologic cancer cohort only (dose escalation and dose expansion cohorts)
Recurrent or progressive disease within 30 days of the last dose of weekly
paclitaxel or nab-paclitaxel
NOTE: Patients with recent minor surgical procedures with minimal risk for wound healing
complications may register =< 6 weeks after the procedure with documented approval by the
surgical team
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