Safety and Pharmacokinetic Profiles of Two Formulations of CO-1.01 in Patients With Advanced Solid Tumors

Clovis Oncology

Status and phase

Completed

Phase 1

Conditions

Advanced Solid Tumor

Treatments

Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)

Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01392976

CO-101-004

Details and patient eligibility

About

The purpose of this study is to compare the pharmacokinetic and safety profiles of two formulations of CO-1.01 in patients with Advanced Solid Tumors.

Full description

Gemcitabine is used alone or in combination with other chemotherapy as a treatment for several solid tumor types, including pancreatic cancer, NSCLC, and ovarian cancer. Unfortunately, many patients fail to derive benefit from this treatment. No clinical or molecular marker has been established to predict benefit from gemcitabine therapy, so patients are treated empirically until evidence of disease progression or worsening performance status.

The potential for human equilibrative nucleoside transporter-1 (hENT1) expression to predict survival in gemcitabine-treated patients has been studied, and data suggest that patients with low levels of tumor cell hENT1 expression derive less benefit from gemcitabine treatment than patients with high levels of tumor cell hENT1 expression. Furthermore, the PK profiles of CO-1.01 and gemcitabine are different, and this may also favorably influence the in vivo antiproliferative effects of CO-1.01. These data support the hypothesis that patients expressing low levels of hENT1 will derive minimal benefit from gemcitabine, but will receive benefit from CO-1.01 (gemcitabine elaidate) which enters tumor cells in a hENT1-independent fashion.

The formulation of CO-1.01 that is currently used in clinical studies contains 15 mg/mL of gemcitabine-5'-elaidate solubilized in purified phospholipids. Recently, Clovis Oncology developed a 30 mg/ml formulation which will be characterized in this study.

Enrollment

17 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis with a histologically confirmed solid tumor malignancy that is metastatic or unresectable for which there is no standard curative or palliative treatment option 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
Written consent on an Institutional Review Board/Independent Ethics Committee-approved IC Form prior to any study-specific evaluation

Exclusion criteria

Clinically significant abnormal 12-lead ECG or QTcF>450msec (males) or >470 msec (females), PR>240 msec, or a QRS>110msec
Family history of long QT syndrome
Implantable pacemaker or implantable cardioverter defibrillator
Symptomatic brain metastases
Concomitant treatment with prohibited medications
Treatment with a previous regimen of CO-1.01 within 30 days or randomization
Treatment with any medication known to produce QT prolongation
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 of 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