Advanced Solid TumorPhase 1NCT01392976
Safety and Pharmacokinetic Profiles of Two Formulations of CO-1.01 in Patients With Advanced Solid Tumors
A Phase 1 study testing CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) and CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) in people with Advanced Solid Tumor, run by Clovis Oncology, Inc. at 3 sites in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) and CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesNetherlands
- Study dates
- Apr 2011to Apr 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
The Netherlands Cancer Institute
Amsterdam, 1066 CX
Maastricht University Medical Center
Maastricht, 6229 HX
University Medical Center Utrecht
Utrecht, 3584 CX
About this study
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
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.
Read the 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.
- Conditions
- Advanced Solid Tumor
- Being tested
- CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids), CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)
- Keywords
- cancer, advanced, solid, tumor, gemcitabine, human equilibrative nucleoside transporter-1 (hENT1), CO-1.01, CO-101, CO101
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids)Drug
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 1 and Day 8 for Treatment Sequence 2.
CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids)Drug
1250 mg/m2 intravenous infusion on Day 1 for Treatment Sequence 2 and Day 8 for Treatment Sequence 1.
| Study group | Role | What they receive |
|---|---|---|
| CO-1.01 Formulation B | Experimental | Not described Receives: Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) |
| CO-1.01 Formulation A | Active comparator | Not described Receives: Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of the AUC0-∞ of the two formulations of CO-1.01 given as a 30 min i.v. infusion at 1250 mg/m2
Measured: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8
Secondary outcomes (4)
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
Measured: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8
QT/QTc interval of the ECG
Measured: 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
Measured: 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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2011 (estimated)
- Study startApr 2011
- Primary completionOct 2011
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clovis Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jan Schellens, MD PhD, Principal investigator, The Netherlands Cancer Institute, Amsterdam, Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01392976
- Sponsor's protocol ID
- CO-101-004
- Status last verified
- Aug 2014
- First submitted
- 13 Apr 2011
- Last updated
- 15 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01392976
- Acronym / sponsor ID
- CO-101-004
- Conditions
- Advanced Solid Tumor
- Keywords
- cancer, advanced, solid, tumor, gemcitabine, human equilibrative nucleoside transporter-1 (hENT1), CO-1.01, CO-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Clovis Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 13 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CO-1.01 Formulation B | Experimental | Drug: CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) |
| CO-1.01 Formulation A | Active comparator | Drug: CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | CO-1.01 Formulation A |
| 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. | Drug | CO-1.01 Formulation B |
Primary outcome
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
4 secondary outcomes
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Schellens, MD PhD principal investigator
The Netherlands Cancer Institute, Amsterdam, Netherlands
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CO-1.01 Formulation A (Aqueous suspension containing 15 mg/mL of drug solubilized in purified phospholipids) and CO-1.01 Formulation B (Aqueous suspension containing 30 mg/mL of drug solubilized in purified phospholipids) in people with Advanced Solid Tumor, run by Clovis Oncology, Inc. at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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 (time frame: Serum & urine PK sampling at multiple timepoints through Cycle 1: Day 1 & Day 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2014; AzTrials last refreshed its copy on 8 Nov 2026.