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

Overview

About this study

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, gynecological cancers, or other malignancies that cannot be removed by surgery. 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 or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel albumin-stabilized nanoparticle formulation and bevacizumab may kill more tumor cells.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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:

- Histologic proof of endometrial cancer including endometrioid, serous, clear
cell, mucinous, undifferentiated, mixed, and carcinosarcoma histologies

- 1-3 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

- 1-4 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

- If 1 or 2 prior lines of chemotherapy, patient's disease must be
platinum-resistant

- NOTE: Platinum-resistance is defined as any of the following occurring
< 183 days after the last dose of platinum-based chemotherapy:

- Development of measurable disease (per Response Evaluation
Criteria in Solid Tumors [RECIST] 1.1)

- Progression of radiographic disease (per RECIST 1.1)

- 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)

- 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

- Increase in CA-125 level to >= 2 x nadir (if nadir > ULN)

- 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

- 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
bevacizumab

- Dose escalation cohort: For ovarian, fallopian tube, and peritoneal cancers only: Must
meet criteria for one option below:

- 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)

- Prior allergic reaction to carboplatin or cisplatin

- 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 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

- NOTE: exception for patients with metastatic uveal or mucosal melanoma for which
there are no effective/approved front line systemic treatments

- Hemoglobin >= 9.0 g/dL (patients may be transfused to meet hemoglobin [Hgb]
requirement) (obtained =< 14 days prior to registration)

- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to
registration)

- Platelet count (PLT) >= 100,000/mm^3 (obtained =< 14 days prior to registration)

- Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 0.4 mg/dL (obtained =< 14 days
prior to registration)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =<
2.5 x ULN (obtained =< 14 days prior to registration)

- Creatinine =< 1.5 x ULN (obtained =< 14 days prior to registration)

- Alkaline phosphatase =< 2.5 x ULN (obtained =< 14 days prior to registration)

- Absence of proteinuria at screening as demonstrated by one of the following (obtained
=< 14 days prior to registration):

- 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 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

- 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.

- Any anti-cancer therapy or investigational agents =< 4 weeks prior to registration

- 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

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- 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
unknown:

- Pregnant persons

- Nursing persons

- Persons 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

- 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)

- 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

- History of inflammatory bowel disease requiring ongoing therapy

- History of diverticulitis or pancreatitis =< 6 months prior to registration

- History of grade 3 or 4 bowel toxicity from immune checkpoint inhibitor =< 12 weeks
prior to registration

- Invasive surgery =< 6 weeks prior to registration, or planned elective invasive
surgery during study treatment.

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/30/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Matthew Block, M.D., Ph.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Gerardo Colon-Otero, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Kristina Butler, M.D., M.S.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

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