Clinical Trials

Inclusion Criteria:

• Patients with histologically confirmed locally advanced or metastatic solid carcinomas that are likely to over express caprin-1 and have already received or been considered for all therapies known to confer clinical benefit:
  • Patients eligible for the Dosing Schedule Cohort must have histologically confirmed, locally advanced or metastatic colon cancer;
  • Patients eligible for the Cholangiocarcinoma Cohort must have histologically confirmed, locally advanced or metastatic cholangiocarcinoma;
  • Patients eligible for the Expansion Cohort must have histologically confirmed, locally advanced or metastatic colon, gastric, ovarian, bladder cancers, as well as cholangiocarcinomas or hepatomas.
• Tumor progression after receiving standard/approved chemotherapy or where there is no approved therapy or not amenable to a curative treatment.
• Measurable disease per RECIST 1.1 (primary or metastases).
• Karnofsky performance status ≥ 70%.
• Life expectancy of at least 3 months.
• Age ≥ 18 years.
• Signed, written IRB-approved informed consent.
• A negative pregnancy test (if female of childbearing potential).
• Body weight ≤ 100kg in the Dose Escalation Cohort, the 30 mg/kg Dosing Schedule Cohort and the Expansion Cohort if dosing will occur at the 30 mg/kg level.
• Acceptable liver function:
  • Bilirubin ≤ 1.5 times upper limit of normal;
  • AST (SGOT), ALT (SGPT) and Alkaline Phosphatase ≤ 2.5 times upper limit of normal (if  liver metastases are present, then ≤ 5 x ULN is allowed).
• Acceptable renal function:
  • Serum creatinine ≤ upper limit of normal, and calculated creatinine clearance (MDRD or CKDEPI) ≥ 60 mL/min/1.73 m2.
• Acceptable hematologic status:
  • Granulocyte ≥ 1500 cells/mm3;
  • Platelet count ≥ 100,000 (plt/mm3);
  • Hemoglobin ≥ 9 g/dL.
• Urinalysis:
  • No clinically significant abnormalities.
• Acceptable coagulation status:
  • For the Dose Escalation Cohort which completed enrollment November 2017
    • PT ≤ within normal limits;
    • PTT ≤ within normal limits.
  • For the Dosing Schedule Cohort, the Cholangiocarcinoma Cohort and the Expansion Cohort
    • INR≤1.5 times upper limit of normal.
• For men and women of child-producing potential, the use of effective contraceptive methods during the study and up to 6 months after the last dose of TRK-950
• Availability of archived tumor tissue from primary tumor or metastatic disease (if applicable) for caprin-1 determination.
  • For the Dose Escalation Cohort which completed enrollment November 2017, if archival tissue was obtained more than 1 year prior to screening a new biopsy was required to obtain tissue.
  • For the Dosing Schedule Cohort, if archival tissue is available from a biopsy less than 18 month prior to screening this should be collected. If archival tissue is more than 18 months prior to screening, tumor tissue for caprin-1 determination will be obtained with the pre-treatment biopsy.
  • For the Cholangiocarcinoma Cohort if archival tissue is available from a biopsy less than 18 month prior to screening this should be collected.
• If archival tissue was obtained more than 18 months prior to screening a new biopsy will be required to obtain tissue. However, if the patient agrees to the (optional) pre-treatment biopsy, tumor tissue for caprin-1 determination will be obtained from that biopsy.
  • For the Expansion Cohort, if archival tissue is available from a biopsy less than 18 month prior to screening this should be collected. If archival tissue was obtained more than 18 months prior to screening a new biopsy will be required to obtain tissue.

Exclusion Criteria:

• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
• Body weight > 100kg in the Dose Escalation Cohort, the 30 mg/kg Dosing Schedule Cohort and the Expansion Cohort if dosing will occur at the 30 mg/kg level.
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
• Pregnant or nursing women.
  • NOTE: Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry, for the duration of study participation and up to 6 months after the last dose of TRK-950. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within four weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C).
• Unwillingness or inability to comply with procedures required in this protocol.
• Known active infection with HIV, hepatitis B, hepatitis C.
• Symptomatic brain metastases. Patients with asymptomatic brain metastases may be enrolled provided they do not require steroids and have been off steroid for a least 2 weeks prior to day 1 of cycle 1.
• 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.
• Patients who are currently receiving any other investigational agent.