Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
TP-1287 is an oral phosphate prodrug of the CDK9 inhibitor, alvocidib. This is a Phase 1,
open-label, dose-escalation, dose-expansion, safety, pharmacokinetics, and pharmacodynamic
study, with a purpose of determining the maximum tolerated dose (MTD) and dose-limiting
toxicities (DLTs) of oral TP-1287 in patients with advanced metastatic or progressive solid
tumors who are refractory to, or intolerant of, established therapy known to provide clinical
benefit for their condition.
Phase
Phase 1
Funding Agency/Sponsor
Industrial
Disease
Bone and Soft Tissue Cancers
Enrollment Eligibility
Inclusion Criteria:
1. For Dose Escalation:
1. Have a histologically confirmed diagnosis of advanced metastatic or progressive
solid tumor excluding tumor types with rapid cell turnover, ie, small cell cancer
(lung and extra pulmonary), inflammatory breast cancer (IBC), medulloblastoma,
neuroblastoma and melanoma with extensive liver metastasis (greater than or equal
to 50% of the liver involved; patients with melanoma and metastasis to less than
50% of the liver are eligible)
2. Be refractory to, or intolerant of, established therapy known to provide clinical
benefit for their condition.
2. For Dose Expansion:
1. Patients who have histologically confirmed locally advanced or metastatic
unresectable Ewing sarcoma
2. Have received at least one prior line of treatment (but no more than 5 prior
lines) including an anthracycline.
3. Have one or more measurable tumors measurable or evaluable as outlined by modified
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or
equal to 1
5. Have a life expectancy greater than or equal to 3 months at the time of informed
consent/assent.
6. Be greater than or equal to 18 years of age for dose escalation and expansion;
Patients with Ewing sarcoma aged ≥ 12 years may also participate in dose expansion if
they weigh ≥40 kg
7. Have a negative pregnancy test (if female of childbearing potential)
8. Have acceptable liver function:
1. Bilirubin less than or equal to 1.5x upper limit of normal (ULN) (unless
attributed to Gilbert's syndrome)
2. Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and
alkaline phosphatase less than or equal to 2.5x upper limit of normal (ULN) *If
liver metastases are present, then less than or equal to 5x ULN is allowed.
- If bone metastases are present, but bilirubin, AST, ALT are ≤2.5x ULN, then
there is no upper limit for alkaline phosphatase level. Radiographic proof
of bone involvement is required, and alkaline phosphatase fractionation is
strongly recommended to confirm the elevation is due to bony metastases.
9. Have acceptable renal function:
a. Calculated creatinine clearance greater than or equal to 30 mL/min
10. Have acceptable hematologic status:
1. Granulocyte greater than or equal to 1500 cells/mm3
2. Platelet count greater than or equal to 100,000 (plt/mm3)
3. Hemoglobin greater than or equal to 8 g/dl
11. Have acceptable coagulation status:
1. Prothrombin time (PT) within 1.5x normal limits
2. Activated partial thromboplastin time (aPTT) within 1.5x normal limits
12. 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 and for the duration of study participation including for at least 3
months (males) and 6 months (females) after the last dose of study drug. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately.
13. Male patients must agree not to donate sperm during the study and for 3 months after
the last dose of TP-1287 due to unknown risks and potential harm to an unborn
child/infant.
14. Female patients must agree not to donate eggs during the study and for 6 months after
the last dose of TP-1287 due to unknown risks and potential harm to an unborn
child/infant.
15. 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
re-screened for study participation or a protocol amendment alters the care of an
ongoing patient, a new ICF must be signed.) Assent is also required for patients who
have not attained the legal age of consent for treatments or procedures involved in
research.
Exclusion Criteria:
1. History of congestive heart failure (CHF), greater than New York Heart Association
(NYHA) Class III, myocardial infarction within the past 6 months prior to Cycle 1 Day
1, left ventricular ejection fraction (LVEF) less than 45% by echocardiogram (ECHO) or
multigated acquisition scan (MUGA), uncontrolled unstable arrhythmia, 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. Presence of symptomatic central nervous system metastatic disease or disease that
requires local therapy such as radiotherapy, surgery, or increasing dose of steroids
within the prior 2 weeks. Patients with previously treated and/or controlled
metastasis are eligible.
5. Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting
02 saturation of less than or equal to 90% breathing room air)
6. Have undergone major surgery within 2 weeks prior to Cycle 1 Day 1
7. Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy
8. Are pregnant or nursing
9. Received treatment with surgery, chemotherapy, or investigational therapy within 28
days or 5 half-lives, whichever occurs first, prior to first administration of study
drug (6 weeks for nitrosoureas or Mitomycin C) and 2 weeks for radiation therapy.
10. Are unwilling or unable to comply with procedures required in this protocol
11. Have known infection with human immunodeficiency virus (HIV), hepatitis B, or
hepatitis C. Patients with history of chronic hepatitis that is currently not active
are eligible.
12. Have a serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other
conditions) that could compromise protocol objectives in the opinion of the
investigator and/or the sponsor
13. Are currently receiving any other investigational agent
14. Have exhibited allergic reactions to a similar structural compound, biological agent,
or formulation
15. Have symptomatic malabsorption conditions (eg, Crohn's disease, etc) 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