A phase I, open-label, two-stage, randomized, crossover, comparative pharmacokinetic and safety study of two formulations of CO-1.01 for injection in patients with advanced solid tumors.

Completed

Conditions: advanced solid neoplasm
advanced solid tumors
10027655

Registration Number: NL-OMON34352

Lead Sponsor: Clovis Oncology Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 21

Inclusion Criteria

Patients must satisfy all of the following criteria:
• Diagnosis with a histologically confirmed solid tumor malignancy that is metastatic or unresectable for which there are no standard curative or palliative treatment options available and for which CO-1.01 treatment would be appropriate
• Life expectancy of at least 3 months
• Performance Status (ECOG) 0 or 1
• Age >=18 years
• Adequate hematological and biological function, confirmed by the following laboratory values:
Bone Marrow Function
* Absolute neutrophil count (ANC) >=1.5 × 109/L
* Platelets >100.0 × 109/L
* Hemoglobin >=9 g/dL (or 5.6 mmol/L)
Hepatic Function
* AST <= 3 × upper limit of normal (ULN); if liver metastases, <=5 × ULN
* Bilirubin <=2 × ULN
* Albumin >3 g/dL (or 30 g/L)
Renal Function
*Serum creatinine <=1.5 × ULN
• Written consent on an Institutional Review Board/Independent Ethics Committee-approved IC Form prior to any study-specific evaluation

Exclusion Criteria

Any of the following criteria will exclude patients from study participation:
• Clinically significant abnormal 12-lead ECG or QTcF >450 msec (males) or >470 msec (females), PR >240 msec, or a QRS >110 msec
• Family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Symptomatic brain metastases
• Concomitant treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment [except corticosteroids and megesterol acetate], or immunotherapy) <=14 days prior to CO-1.01
• Treatment with a previous regimen of CO-1.01 within 30 days of randomization
• Treatment with any medication known to produce QT prolongation (see Appendix 4)
• Surgical procedures are not allowed <=14 days prior to administration of CO 1.01. in all cases, the patient must be sufficiently recovered and stable
• History of allergy to gemcitabine or eggs
• Females who are pregnant or breastfeeding
• Refusal to use adequate contraception for fertile patients (females and males) for 6 months after the last dose of CO-1.01
• Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including active infection, arterial thrombosis, and symptomatic pulmonary embolism)
• Any other reason the investigator considers the patient should not participate in the study

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>•Ratio of the AUC0-* of the two formulations of CO-1.01 given as a 30 min i.v.<br /><br>infusion at 1250 mg/m2 </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>•PK of CO-1.01 and metabolites in plasma and urine after 1250 mg/m2 CO-1.01<br /><br>given as a single 30 min i.v. infusion<br /><br>•QT/QTc interval of the ECG<br /><br>•Relationship between plasma concentration of CO-1.01 and QT/QTc interval of<br /><br>the ECG<br /><br>•Drug tolerability and toxicity using clinical AE monitoring and clinical<br /><br>laboratory testing<br /><br><br /><br>Exploratory<br /><br>•Tumor response (according to RECIST 1.1)<br /><br>•Blood concentrations of total cholesterol, LDL cholesterol, HDL cholesterol,<br /><br>and triglycerides</p><br>