Clinical trial NCT01251562: Safety Study of Sterile Compound C31510 for Injection to Subjects With Solid Tumors
Official title: A Phase 1 Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Sterile Compound c31510 for Injection Administered Intravenously to Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: BPGbio
Sponsor class: INDUSTRY
First posted: 2010-12-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Tumor Assessment
timeFrame: at baseline and then once every two treatment cycles of 28 days (2 months) thereafter in the absence of clinical rapid progression of disease.
Secondary outcomes:
measure: blood samples taken for plasma pharmacokinetics (PK) evaluation
timeFrame: 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
measure: blood samples taken for plasma pharmacodynamics evaluation
timeFrame: 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.
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
Study officials:
References: