| Eligibility |
Inclusion Criteria:
- Female participants who are at least 18 years of age.
- Signed written informed consent.
- A histology confirming diagnosis of high grade serous ovarian/peritoneal/fallopian
tube cancers and platinum-resistant disease as defined as disease progression on a
platinum-containing agent or recurrent within 180 days of prior dose of a
platinum-containing chemotherapeutic regimen will be enrolled in this study. Pathology
must have been reviewed at MD Anderson.
- A female participant is eligible to participate if at least one of the following
conditions applies:
- Not a woman of childbearing potential (WOCBP) OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 5 months after the last dose of study treatment.
- Measurable disease is present as defined by modified Response Evaluation Criteria in
Solid Tumors (RECIST) version (v) 1.1 criterion, and there is disease present in the
peritoneal cavity or retroperitoneal lymph nodes. Disease outside the peritoneal
cavity is allowed as long as metastases are present within the peritoneal cavity or
retroperitoneum.
- Adequately controlled blood pressure (BP) with or without antihypertensive
medications, defined as BP less than or equal to 150/90 mmHg at screening and no
change in antihypertensive medications within 1 week prior to the start of treatment.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Ability to understand and willingness to sign informed consent form prior to
initiation of the study and any study procedures.
- Participants willing to undergo intraperitoneal port placement and scheduled
peritoneal fluid and peripheral blood draws.
- Absolute neutrophil count (ANC) >= 1500/uL (within 10 days prior to start of study
treatment)
- Platelets >= 100,000/uL (within 10 days prior to start of study treatment)
- Hemoglobin >= 9.0 g/dL (transfusion is allowed) (within 10 days prior to start of
study treatment)
- Criteria must be met without erythropoietin dependency and without packed red
blood cell (pRBC) transfusion within last 2 weeks of the screening test.
Participants may be on a stable dose of erythropoietin (>= approximately 3
months).
- Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) >= 30
mL/min for participants with creatinine > 1.5 x ULN (within 10 days prior to start of
study treatment)
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total
bilirubin levels > 1.5 x ULN (within 10 days prior to start of study treatment)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x
ULN (=< 5 x ULN for participants with liver metastases) (within 10 days prior to start
of study treatment)
- International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless
participant is receiving anticoagulant therapy as long as PT or activated partial
thromboplastin time (aPTT) is within therapeutic range of intended use of
anticoagulants (within 10 days prior to start of study treatment)
Exclusion Criteria:
- Is pregnant, breastfeeding, or expecting to conceive within the projected duration of
the study, starting with the screening visit through 120 days after the last dose of
trial treatment. If a WOCBP who has a positive urine pregnancy test within 72 hours
prior to randomization that cannot be confirmed as negative, a serum pregnancy test
will be required.
- Has received prior therapy with lenvatinib
- Has received systemic anti-cancer therapy including investigational agents (e.g.
anti-vascular endothelial growth factor (VEGF) or immune checkpoint inhibitor therapy)
within 4 weeks of the first planned dose of investigational therapy.
- Participants must have recovered from all adverse events (AEs) due to previous
therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy,
alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the
principal investigator. If a participant received major surgery, they must have
recovered adequately from the toxicity and/or complications from the intervention
prior to starting study treatment. Additionally, lenvatinib should not be administered
for at least two weeks following major surgery and until adequate wound healing.
- Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=< 2 weeks of radiotherapy) to noncentral nervous system
(CNS) disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention. Participants who have entered the follow-up phase of an
investigational study may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
- Has history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years. The time requirement does not
apply to participants who underwent successful definitive resection of basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder
cancer, in situ cervical cancer, or other in-situ cancers.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study intervention.
- Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of chronic hepatitis B or hepatitis C virus infection.
- Has a known history of active Bacillus tuberculosis (TB)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- Has had an allogenic tissue/solid organ transplant.
- Participants having greater than 1+ proteinuria on urinalysis will undergo 24-hour (h)
urine collection for assessment of proteinuria. Participants with urine protein
greater than or equal to 2 g/24-h will be ineligible.
- Has a left ventricular ejection fraction (LVEF) below the institutional (or local
laboratory) normal range, as determined by multigated acquisition (MUGA) or
echocardiogram (ECHO).
- Has clinically significant cardiovascular disease within 12 months from first dose of
study intervention, including New York Heart Association (NYHA) class III or IV
congestive heart failure, unstable angina, myocardial infarction, cerebral vascular
event, or cardiac arrhythmia associated with hemodynamic instability. Note: medically
controlled arrhythmia would be permitted.
- Prolongation of corrected QT using Fridericia's formula (QTcF) interval to > 480 ms
- Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. Subject
with known deep vein thrombosis/pulmonary embolism that are under appropriate
anti-coagulation treatment are eligible.
- Has radiographic evidence of tumor encasement or invasion of a major blood vessel, or
intra-tumoral cavitation.
- Any history of hypertensive crisis with prior anti-VEGF therapy.
- Have pre-existing >= grade 3 gastrointestinal or non-gastrointestinal fistula
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