| Eligibility |
Inclusion Criteria:
1. Patients to be enrolled during Dose Escalation with capsules must have a
histologically confirmed diagnosis of advanced metastatic or progressive solid tumor
who are refractory to, or intolerant of, established therapy known to provide clinical
benefit for their condition (enrollment complete).
2. Following approval of Amendment 5.0, patients to be enrolled during Dose Escalation
with Tablets must have a histologically confirmed diagnosis of anal cancer and:
1. have received at least one line of systemic platinum-based therapy in the
advanced setting; (Note: Systemic platinum therapy given in the adjuvant setting
will meet this criterion if there is recurrence or metastasis within 6 months of
completing adjuvant therapy.); and
2. have received no more than 3 total lines of systemic therapy in the advanced
setting.
3. Have measurable disease as outlined by the Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of =1
5. Be =18 years of age
6. Have a negative pregnancy test (if female of childbearing potential)
7. Have acceptable liver function:
1. Bilirubin =1.5x upper limit of normal (ULN) (unless associated with Gilbert
syndrome)
2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and
alkaline phosphatase =2.5x ULN* *If liver metastases are present, then = 3x ULN
is allowed.
8. Have acceptable renal function: calculated creatinine clearance =60 mL/min (using
Cockcroft Gault formula)
9. Have acceptable hematologic status:
1. Granulocyte =1500 cells/mm3
2. Platelet count =100,000 (plt/mm3)
3. Hemoglobin =8 g/dL
10. Have acceptable coagulation status:
1. International Normalized Ratio (INR) or Prothrombin time (PT) within 1.5x normal
limits unless the patient is receiving anticoagulant therapy, in which case, the
patient's PT or partial thromboplastin time (PTT) must be within the therapeutic
range of intended use for their anticoagulant.
2. Partial activated partial thromboplastin time (aPTT) or activated partial
thromboplastin time (aPTT) within 1.5x normal limits unless the patient is
receiving anticoagulant therapy, in which case, the patient's PT or PTT must be
within the therapeutic range of intended use for their anticoagulant.
11. Be nonfertile or agree to use an adequate method of contraception. Sexually active
patients and their partners must use a highly effective method of contraception prior
to study entry for the duration of study participation and for at least 3 months
(males) and 6 months (females) after the last study drug dose.
12. Male patients only: must agree not to donate sperm during the study and for 3 months
after the last dose of TP-1454.
13. Women of childbearing potential must agree not to donate eggs during the study and for
6 months after the last dose of TP-1454.
14. Have read and signed the Institutional Review Board (IRB)-approved informed consent
form (ICF) prior to any study-related procedure. (In the event that the patient is
rescreened for study participation or a protocol amendment alters the care of an
ongoing patient, a new ICF must be signed.)
15. Dose escalation in mSCCA with tablets only: Patients who are HIV+ may be enrolled if
the following conditions are met:
1. CD4+ T-cell count = 300/µL
2. No opportunistic infection within the past 12 months
3. Treatment with established antiretroviral therapy for at least 4 weeks with a
viral load < 400 copies/mL prior to first dose with TP-1454.
16. Dose escalation in mSCCA with tablets only: Patients who have had hepatitis B or C
viral infections (HBV or HCV, respectively) may be enrolled if the following
conditions are met:
1. Have completed or are undergoing curative antiviral treatment with viral load
below the limit of quantification
2. Test positive for antibody and negative for viral RNA
Exclusion Criteria:
1. New York Heart Association Class III or IV cardiac disease, or myocardial infarction,
severe unstable angina, coronary/peripheral artery bypass graft, congestive heart
failure within the past 6 months or evidence of ischemia on electrocardiogram (ECG)
within 14 days prior to Cycle 1/Day 1
2. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >450
msec in men and >470 msec in women
3. Have a seizure disorder requiring anticonvulsant therapy
4. Have untreated central nervous system (CNS) metastases including carcinomatous
meningitis. Patients with definitively treated (radiotherapy or surgery) CNS
metastases may be eligible if asymptomatic and not receiving corticosteroids in excess
of prednisone 10 mg (or equivalent) per day for =2 weeks before first dose of TP-1454
5. Have hypoxemia (defined as resting O2 saturation of =90% breathing room air)
6. Have symptomatic interstitial lung disease
7. Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1
8. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy
9. Are pregnant or nursing
10. Received treatment with radiation therapy to a target lesion, surgery, chemotherapy,
or investigational therapy within 28 days or 5 half-lives, whichever occurs first,
prior to study entry (6 weeks for nitrosoureas or mitomycin C)
11. Are unwilling or unable to comply with procedures required in this protocol
12. Dose escalation in solid tumors with capsules only: Have known infection with
hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is
currently not active are eligible
13. Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
Investigator and/or the Sponsor
14. Are currently receiving any other investigational agent
15. Have exhibited allergic reactions to a similar structural compound, biological agent,
or formulation(s)
16. Have malabsorption conditions or have undergone significant surgery to the
gastrointestinal tract that could impair absorption or that could result in short
bowel syndrome with diarrhea due to malabsorption
17. Have a history of malignancy within the past 24 months except curatively treated in
situ cancers
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