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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01392976
First Posted: July 13, 2011
Last Update Posted: August 15, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Clovis Oncology, Inc.
  Purpose
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.

Condition Intervention Phase
Advanced Solid Tumor Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2 [ Time Frame: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8 ]

Secondary Outcome Measures:
  • PK of CO-1.01 and metabolites in plasma and urine after 1250 mg/m2 CO-1.01 given as a single 30 min i.v. infusion [ Time Frame: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8 ]
  • QT/QTc interval of the ECG [ Time Frame: Continuous ECG monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1: D1, D8 ]
  • Relationship between plasma concentration of CO-1.01 and QT/QTc interval of the ECG [ Time Frame: Plasma: multiple timepoints through C1D1 and D8. ECG: continuous monitoring 8 hrs pre & post dose C1: D1, D8. 12 lead ECGs pre-dose, 30mins, 24hr, 48hr, 72hr C1:D1, D8. ]
  • Drug tolerability and toxicity using clinical AE monitoring and clinical laboratory testing [ Time Frame: From the time of signing the ICF until 28 days after last dose of CO-101. CO-101 dosed on C1D1, C1D8, C1D15, C2D1, C2D8, and C2D15. ]

Enrollment: 17
Study Start Date: April 2011
Study Completion Date: April 2013
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CO-1.01 Formulation B Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 2 and Day 8 for Treatment Sequence 1.
Active Comparator: CO-1.01 Formulation A Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids)
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 1 and Day 8 for Treatment Sequence 2.

Detailed 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01392976


Locations
Netherlands
The Netherlands Cancer Institute
Amsterdam, Netherlands, 1066 CX
Maastricht University Medical Center
Maastricht, Netherlands, 6229 HX
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
Clovis Oncology, Inc.
Investigators
Principal Investigator: Jan Schellens, MD PhD The Netherlands Cancer Institute, Amsterdam, Netherlands
  More Information

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT01392976     History of Changes
Other Study ID Numbers: CO-101-004
First Submitted: April 13, 2011
First Posted: July 13, 2011
Last Update Posted: August 15, 2014
Last Verified: August 2014

Keywords provided by Clovis Oncology, Inc.:
cancer
advanced
solid
tumor
gemcitabine
human equilibrative nucleoside transporter-1 (hENT1)
CO-1.01
CO-101
CO101