Know Cancer

forgot password

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

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumor

Thank you

Trial Information

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

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.

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2

Outcome Time Frame:

Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8

Safety Issue:


Principal Investigator

Jan Schellens, MD PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Netherlands Cancer Institute, Amsterdam, Netherlands


United States: Food and Drug Administration

Study ID:




Start Date:

April 2011

Completion Date:

Related Keywords:

  • Advanced Solid Tumor
  • cancer
  • advanced
  • solid
  • tumor
  • gemcitabine
  • human equilibrative nucleoside transporter-1 (hENT1)
  • CO-1.01
  • CO-101
  • CO101
  • Neoplasms