Inclusion Criteria:
- - Subjects aged ≥ 18 years.
- - Cohort A (Neuroendocrine Tumor) Only:
---Subjects with well differentiated neuroendocrine tumors who are either on a
watch- and-wait approach or receiving treatment with somatostatin analog(s).
Patient
who received and completed another active treatment but are on a "break" from
treatment will be allowed to enroll (e.g., patients that had completed PRRT).
- - Cohort B (Gynecological Cancer) Only:
---Subjects with early-stage (I or II) ovarian/fallopian-tube cancer in surveillance
who have completed all treatment or are receiving adjuvant treatment with
platinum-based chemotherapy +/- maintenance therapy with PARP inhibitor(s) or
bevacizumab.
---Subjects with endometrial cancer which is low risk, low-intermediate risk in
surveillance, or high-intermediate risk receiving brachytherapy. Risk category is
based on GOG criteria.
- - ECOG Performance Status ≤ 2.
- - Documentation of a score of 4 or higher when answering either of the
NCCN-recommended screening questions ("How exhausted do you feel on a scale of 0 to
10?" or "How impaired do you feel by this fatigue on a scale of 0 to 10?") within 4
weeks prior to randomization.
- - Adequate organ function as defined as:
- Hematologic:
- Hemoglobin ≥ 9 g/dL.
- - Hepatic:
- Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Subjects with liver
metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
- - Renal:
---Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
- - For female subjects: Negative pregnancy test or evidence of post-menopausal
status.
The post-menopausal status will be defined as having been amenorrheic
for 12 months without an alternative medical cause. The following age-specific
requirements apply:
- - Women < 50 years of age:
----Amenorrheic for ≥ 12 months following cessation of exogenous hormonal
treatments; and luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution; or.
----Underwent surgical sterilization (bilateral oophorectomy or
hysterectomy).
- - Women ≥ 50 years of age:
- Amenorrheic for 12 months or more following cessation of all
exogenous hormonal treatments and luteinizing hormone and
follicle-stimulating hormone levels in the post-menopausal range for
the institution; or Amenorrhea for 24 months following cessation of
all exogenous hormonal treatments, if applicable; or.
- - Had radiation-induced menopause with last menses >1 year ago; or.
- - Had chemotherapy-induced menopause with last menses >1 year ago; or.
- - Underwent surgical sterilization (bilateral oophorectomy, bilateral
salpingectomy, or hysterectomy).
- - Female subjects of childbearing potential and male subjects with a sexual
partner of childbearing potential must agree to use a highly effective method
of contraception.
- - Able to provide informed consent and willing to sign an approved consent form
that conforms to federal and institutional guidelines.
Exclusion Criteria:
- - For the Neuroendocrine Tumor cohort: Receiving treatment with Cytotoxic
Chemotherapy, Radiation Therapy, PRRT or TKIs within 6 weeks prior to the first dose
of study treatment.
- - For the Gynecological Cancer cohort: Receiving any systemic treatment besides those
listed in Inclusion 3-Cohort B (Gyn only) within 6 weeks prior to the first dose of
study treatment.
- - Untreated or uncontrolled hypothyroidism (TSH must be within institutional normal
limits for age).
- - History of significant autoimmune disease in the opinion of the investigator that is
likely to impact study participation.
- - Prior use of guarana supplements within two months of consent.
- - Self-reported "caffeine sensitivity" defined as excessive unwanted feelings of
anxiousness, jitteriness, difficulty sleeping, or anxiety after caffeine exposure,
which in the opinion of the Investigator is likely to negatively impact study
participation.
- - Concurrent use of psychostimulants (e.g., lisdexamfetamine, methylphenidate).
- - Major surgery within 4 weeks prior to starting study therapy or subjects who have
not fully recovered from major surgery.
- - The diagnosis of another malignancy which, in the opinion of the investigator, is
likely to negatively impact subject safety or study aims.
- - Known brain metastases or cranial epidural disease.
--Note: Subjects with brain metastases or cranial epidural disease adequately
treated with radiotherapy and/or surgery and stable for at least 4 weeks before the
first dose of study treatment will be allowed on trial. Subjects must be
neurologically asymptomatic and without corticosteroid treatment at the time of the
first dose of study treatment.
- - Current evidence of uncontrolled, significant intercurrent illness including, but
not limited to, the following conditions:
--Cardiovascular disorders:
- Significant symptomatic carcinoid heart disease in the opinion of the
investigator.
- - Congestive heart failure New York Heart Association Class III or IV, unstable
angina pectoris, serious cardiac arrhythmias.
- - Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI),
or other ischemic events) within 3 months before the first dose.
- - Thromboembolic events (eg, deep venous thrombosis, pulmonary embolism) within 1
month before the first dose.
- - QTc prolongation defined as a QTcF > 500 ms.
- - Known congenital long QT.
- - Uncontrolled hypertension per investigator assessment or grade 3 hypertension
per CTCAE v.
5.0.
- - Any other condition that would, in the Investigator's judgment, contraindicate
the subject's participation in the clinical study due to safety concerns or
compliance with clinical study procedures (e.g., infection/inflammation,
intestinal obstruction, unable to swallow medication, [subjects may not receive
the therapy through a feeding tube], social/ psychological issues, etc.)
- Known HIV infection with a detectable viral load within 6 months of the anticipated
start of treatment.
--Note: Subjects on effective antiretroviral therapy with an undetectable viral load
within 6 months of the anticipated start of treatment are eligible for this trial.
- - Known active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination, radiographic findings, and TB testing in
line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)
result), or hepatitis C.
--Note: Subjects with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.
- - Medical, psychiatric, cognitive, or other conditions that may compromise the
subject's ability to understand the subject information, give informed consent,
comply with the study protocol or complete the study.
- - Known hypersensitivity or allergy to investigational product (IP).
- - Subjects taking prohibited medications as described in Section 6.6.
2 or medications
for which caffeine intake is contraindicated including: β-adrenergic agonists,
and/or medications that contain pseudoephedrine. A washout period of prohibited
medications for a period of at least five half-lives or as clinically indicated
should occur before the start of treatment.
