Safety Study of Sterile Compound C31510 for Injection to Subjects with Solid Tumors
- Conditions
- Solid Tumors
- Interventions
- Drug: Sterile Compound C31510 for Injection
- Registration Number
- NCT01251562
- Lead Sponsor
- BPGbio
- Brief Summary
The primary objective of this clinical study is as follows:
• To determine the MTD and to assess the safety and tolerability of C31510 administered as a single 4-hour IV infusion (up to nine different dosages) in subjects with solid tumors
The secondary objective of this study is as follows:
• To evaluate plasma PK and estimate renal elimination of C31510 administered as a single 4-hour IV infusion (up to nine different dosages) in subjects with solid tumors
The exploratory objectives of this study are as follows:
* To evaluate the pharmacodynamic correlates of C31510 activity in plasma and peripheral blood cells
* To radiographically evaluate the effects of C31510 on tumors. In selected subjects, the effects on vascular permeability will be assessed by digital contrast enhanced (DCE)-magnetic resonance imaging (MRI)
* To evaluate tumor response (preliminary antitumor activity) after repeat administration of C31510
* Long-term safety and tolerability of C31510 after repeat administration
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- The subject has a histologically confirmed solid tumor that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective.
- The subject is at least 18 years old.
- The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.
- The subject has a life expectancy of greater than 3 months.
- The subject has organ and marrow function as follows: ANC>1500mm3, platelets>100,000 dl, hemoglobin >9 g/dL, bilirubin ≤ 1.5mg/dL, serum creatinine ≤1.5mg/dL or creatinine clearance >60 mL/min, and alanine aminotransferase (ALT), aspartate transaminase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement.
- The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
- Sexually active subjects must use an accepted method of contraception during the course of the study.
- Female patients of childbearing potential must have a negative pregnancy test at enrollment.
- If a subject has received more than three prior regimens of cytotoxic chemotherapy, or more than two biological regimens, or more than 3000cGy to areas containing substantial marrow, the cohort review committee (CRC) must determine subject suitability prior to enrollment.
- The subject has received chemotherapy or radiotherapy within 4 weeks or has received nitrosoureas or mitomycin C within 6 weeks prior to entering the study.
- The subject has received anti-angiogenesis drugs within 4 weeks prior to entering the study.
- The subject has received radiation to ≥25% of his or her bone marrow within 4 weeks of C31510IV treatment.
- The subject has received an investigational drug within 30 days of the first dose of study drug. 6 of 72
- The subject has not recovered to grade ≤1 from adverse events( AEs) due to investigational drugs or other medications, which were administered more than 4 weeks prior to study enrollment.
- The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- The subject is pregnant or lactating.
- The subject is known to be positive for the human immunodeficiency virus (HIV)
- The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
- Must have not taken Vitamin D3 supplements in the last 30 days
- The subject is on HMG-CoA Reductase Inhibitors
- The subject is receiving digoxin, digitoxin, lanatoside C or any type of digitalis alkaloids
- The subject is receiving Colony Stimulating factors. The use of Colony Stimulating factors isf prohibited during the monitoring of DLT in this study.
- The subject is receiving Warfarin.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1 Sterile Compound C31510 for Injection 5.62 mg/kg Sterile Compound C31510 for Injection Cohort 4 Sterile Compound C31510 for Injection 33.0 mg/kg Cohort 9 Sterile Compound C31510 for Injection 139.0 mg/kg Sterile Compound C31510 for Injection Cohort 2 Sterile Compound C31510 for Injection 11.25 mg/kg Sterile Compound C31510 for Injection Cohort 3 Sterile Compound C31510 for Injection 22.5 mg/kg Sterile Compound C31510 for Injection Cohort 5 Sterile Compound C31510 for Injection 44.0 mg/kg Sterile Compound C31510 for Injection Cohort 7 Sterile Compound C31510 for Injection 78.2 mg/kg Sterile Compound C31510 for Injection Cohort 8 Sterile Compound C31510 for Injection 104.3 mg/kg Sterile Compound C31510 for Injection Cohort 6 Sterile Compound C31510 for Injection 58.7 mg/kg Sterile Compound C31510 for Injection
- Primary Outcome Measures
Name Time Method Tumor Assessment at baseline and then once every two treatment cycles of 28 days (2 months) thereafter in the absence of clinical rapid progression of disease. Tumors will be assessed by standard methods ex. computerized tomography (CT), MRI etc; at baseline and then once every two treatment cycles of 28 days (2 months) thereafter in the absence of clinical rapid progression of disease.
Assessment of tumor vascularity (using DCE-MRI) for at least 6 subjects who received C31510 at the MTD, will be done within 24 hours pre-dose and post-dose.
- Secondary Outcome Measures
Name Time Method blood samples taken for plasma pharmacokinetics (PK) evaluation Blood samples collected at pre-dose, post-start of infusion at 0.5, 1, 2, 3.75 (15 min prior to end of infusion), 4.083 (5 min after the end of the infusion) 4.5, 6, 8, 10, and 24 hrs. after the start of the infusion samples are taken to evaluate plasma pharmacokinetics (PK) and estimate renal elimination of C31510 administered as a single IV infusion in subjects with solid tumors
PK will be collected during Day 1 of the first month of each cohort at the following timepoints: pre-dose, post-start of infusion at 0.5, 1, 2, 3.75 (15 min prior to end of infusion), 4.083 (5 min after end of the infusion) 4.5, 6, 8, 10, and 24 hrs. after start of the infusion
Additional PK will be done at pre-dose time and at 24 hours post the dose of Day 3, and on Day 28.blood samples taken for plasma pharmacodynamics evaluation Pharmacodynamic blood samples will be collected pre-dose and at 4 and 24 hours post dose after start of the infusion of Day 1 of each treatment cycle. blood samples are taken to evaluate the pharmacodynamic correlation of C31510 activity in plasma and peripheral blood cells
Trial Locations
- Locations (1)
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States