| Eligibility |
Major inclusion criteria:
1. A histologically or cytologically confirmed solid tumor that is locally advanced,
recurrent, or metastatic; for which curative resection is not currently possible; and
for which systemic treatment with one of the selected anti-cancer agents is a
reasonable therapeutic option.
2. Must be = 18 years of age
3. Has disease such that progression or response to therapy can be evaluated objectively
while on protocol.
4. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Male or female patients of childbearing potential must agree to use contraception or
avoidance of pregnancy measures during the study and for 30 days after the last dose.
6. Females of childbearing potential must have a negative serum pregnancy test.
7. Must have aspartate transaminase (AST) = 2.5 × upper limit of normal (ULN) and alanine
transaminase (ALT) = 2.5 × ULN. Patients who do not have hepatocellular carcinoma but
who have liver lesions or liver metastases may be eligible if AST = 3.5 × ULN and AST
= 3.5 × ULN if agreed upon by the investigator and medical monitor for the sponsor.
8. Hemoglobin (Hgb) = 9 g/dl
9. Total bilirubin = 1.5 × ULN. For patients with liver lesions, total bilirubin = 2.0 ×
ULN may be enrolled if agreed upon by the investigator and medical monitor for the
sponsor
10. Creatinine = 1.5 × ULN or creatinine clearance = 60 mL/min/1.73 m^2 for patients with
creatinine levels above institutional upper limit of normal (using the Cockcroft-Gault
equation).
11. Absolute neutrophil count = 1.5 × 10^9/L
12. Platelets = 100 × 10^9/L
13. Life expectancy = 3 months
Major exclusion criteria:
1. Received anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational
agents within 7 days of first dose of protocol therapy. Patients may begin protocol
therapy on a date determined by the investigator and medical monitor for the sponsor
after a minimum of 7 days since last receiving anti-cancer treatment, provided that
all adverse events related to that have resolved or have been deemed irreversible.
2. Major surgery within 4 weeks prior to first dose; major surgery is defined as a
procedure requiring any of the following: general anesthesia, intubation and
mechanical ventilation, or major incision (e.g., thoracotomy, laparotomy)
3. Any known, untreated, brain metastases. Patients with treated brain metastases must
have no clinical symptoms from the metastases, and must be either off steroids or on a
stable dose of steroids = 10 mg prednisone or equivalent for at least 2 weeks prior to
protocol enrollment. Patients with known leptomeningeal metastases are excluded, even
if treated.
4. Pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study.
5. Significant gastrointestinal disorder(s), in the opinion of the Principal
Investigator, such as active inflammatory bowel disease, extensive gastric or small
intestinal resection (which has resulted in short-gut syndrome or the inability to
take oral medications).
6. Unable or unwilling to swallow either BBI503 daily or an oral selected anti-cancer
therapeutics; or, unwilling to receive intravenous injection of IV anti-cancer
therapeutics.
7. Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface
Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid
(HCV RNA] (qualitative) is detected).
8. Uncontrolled concurrent illness including, but not limited to: ongoing or active
infection requiring therapy, clinically significant non-healing or healing wounds,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia,
significant pulmonary disease (shortness of breath at rest or on mild exertion),
uncontrolled infection or psychiatric illness/social situations that would limit
compliance with study requirements
9. Subjects with a history of another primary cancer with the exception of: a) curatively
resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ;
c) localized prostate cancer not requiring systematic therapy; and d) other primary
cancer with no known active disease present, and no treatment administered in the 2
years prior to enrollment.
10. For patients to be treated with a regimen containing capecitabine: a) Known
hypersensitivity to capecitabine, b) Known dihydropyrimidine dehydrogenase (DPD)
deficiency, c) Significant gastrointestinal disorder(s) that would, in the opinion of
the Investigator, prevent absorption of an orally available agent
11. For patients to be treated with a regimen containing sunitinib: a) Uncontrolled
hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg
despite optimal medical management), b) Evidence of bleeding diathesis or a clinically
significant coagulopathy (= CTCAE Grade 3) within 4 weeks prior to the start of study,
c) Recent hypoglycemia, d) Uncontrolled thyroid dysfunction despite optimal medical
therapy
12. For patients to be treated with a regimen containing doxorubicin: a) Known left
ventricular ejection fraction < 50%, b) Hypersensitivity to doxorubicin
13. A patient to be treated with a regimen containing nivolumab or pembrolizumab will be
excluded if the patient: a) Has an active autoimmune disease requiring
immunosuppression with the exception of subjects with isolated vitiligo, resolved
childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism,
and euthyroid patients with a history of Grave's disease, b) Has had a previous
life-threatening (CTCAE grade 4) immune-mediated adverse reaction; or, a previous
severe (CTCAE grade 3) immune mediated adverse reaction that required treatment with
corticosteroids (more than 10 mg/day prednisone or equivalent dose) for longer than 12
weeks, c) Has a transplanted organ, d) Has interstitial lung disease or active,
non-infectious pneumonitis, e) Has received a live vaccine within 30 days prior to
first dose, f) Previous severe hypersensitivity reaction to another monoclonal
antibody (mAb), g) Has been treated with another monoclonal antibody = 4 weeks before
first dose.
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