A Phase I, Open-Label, Dose Escalation, Multi-Center Study of TPI 287 in Patients With Advanced Malignancies
- Histological or cytological evidence of malignancy
- Patients must have either:
- advanced solid tumors that have recurred or progressed following standard
- Hodgkin's or non-Hodgkin's lymphoma that has recurred or progressed following
standard therapy, have not had a previous bone marrow transplant, and are not
eligible for a bone marrow transplant.
- Failed at least one previous therapeutic regimen and either no longer are candidates
for standard therapy, have no standard therapy available, or choose not to pursue
- Ambulatory with ECOG 0 or 1, and a life expectancy of >3 months.
- Judged by the investigator to have the initiative and means to be compliant with the
protocol and be within geographical proximity to make the required study visits.
- Have ability to read, understand and provide written informed consent for the
initiation of any study related procedures or have a legal representative to perform
- If female, must have a negative pregnancy test within 21 days of start of treatment.
- Agree to the use of an effective method of contraception during the study and for 90
days following the last dose of medication.
- Patients with prior radiation therapy for brain metastasis or primary brain tumors
- Prior radiation therapy or chemotherapy within 4 weeks (6 weeks for prior
nitrosoureas or mitomycin)
- Another active medical condition(s) or organ disease(s) that may either compromise
patient safety or interfere with the safety and/or outcome evaluation of the study
drug. While this exclusion is not limited to the following abnormalities, if any of
the following laboratory abnormalities are present, the patient should be excluded:
- WBC < 3000/uL;
- Absolute neutrophil count < 1500/uL;
- Platelets < 100,000/uL;
- Total bilirubin > 1.5 x upper limit of normal;
- ALT or AST > 3 x upper limit of normal if no liver metastases or >5 upper limit
of normal in the presence of liver metastases;
- Serum creatinine > 1.5 x upper limit of normal;
- INR >2.0.
- Patient has clinically significant cardiac co-morbidities or pulmonary impairment
- Patient or physician plans concomitant chemotherapy, radiation therapy, hormonal
and/or biological treatment for cancer including immunotherapy while on study. Of
note, therapy with LHRH for prostate cancer is acceptable.
- Patient has been treated with any investigational drug, investigational biologic, or
investigational therapeutic device within 30 days of initiating study treatment.
- Tumor appears to involve a major artery or vein.
- Prior or concurrent significant CNS disease including stroke, except for primary or
- Less than 4 weeks since prior major surgery
- Known positive for HIV, Hepatitis B or C
- Concurrent chronic use of aspirin (325 mg/day or more)
- Concurrent or recent (within 1 month) use of thrombolytic agents, or full-dose
anticoagulants (except to maintain patency of preexisting, permanent indwelling IV
catheters) Of note, therapy with low-molecular weight heparin is acceptable as long
as the INR<2.0.
- Uncontrolled hypertension
- Grade II-IV peripheral vascular disease within the past year
- Prior allergic reactions to compounds of similar chemical or biologic composition to
TPI 287, paclitaxel or taxotere, Cremophor-EL-P, or other study agents
- Significant traumatic injury within the past 4 weeks
- Ongoing or active infection requiring parenteral antibiotics or with a fever >38.1°C
within 3 days of the first scheduled day of dosing
- Other concurrent uncontrolled illness which may interfere with the ability of the
patient to participate in the trial
- Patients who are inpatients
- Grade II-IV peripheral neuropathy