Solid TumorPhase 1NCT00968916
Dose Escalation, Safety and Pharmacokinetic Study of AVE8062 in Patients With Solid Tumors
A Phase 1 study testing ombrabulin (AVE8062) in people with Solid Tumor, run by Sanofi at 2 sites in Japan.
Trial summary
Primary objective: To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of AVE8062 administered every 3 weeks in patients with advanced solid tumors. Secondary objectives: To assess the overall safety profile of the drug. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Solid Tumor
- What is being tested?
- ombrabulin (AVE8062)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesJapan
- Study dates
- Sep 2009to Aug 2011
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced solid tumor that has become refractory to conventional treatment or for which no standard therapy exists.
- Patients with signed and dated Institutional Review Board (IRB)-approved patient informed consent form (ICF) prior to enrollment in the study.
Who cannot join
- Eastern Cooperative Oncology Group performance status > or = 2.
- Life expectancy of less than 12 weeks.
- Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study.
- Absence of histologically or cytologically proven cancer.
- Male patients who do not agree with contraception. Absence of negative serum/urinary pregnancy test within the 7 days prior to the enrollment in the study for female patients with childbearing potential. Patients must be post-menopausal, surgically sterile, or using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator).
- Washout period of less than 28 days from prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy) or any investigational treatment, except for nitrosoureas, mitomycin which may not be used up to 42 days prior to the first cycle. No washout period is required for hormonal therapy, however, it must be discontinued before the first cycle.
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- Not recovered from all previous therapies (radiation, surgery, and medications). Adverse events related to previous therapies must be National Cancer Institute Common Terminology Criteria grade < or = 1 (or alopecia < or = grade 2) at screening or returned to the subject's baseline prior to their most recent previous therapy.
- Symptomatic brain metastases and carcinomatous leptomeningitis.
- Other serious illness or medical conditions:
- Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
- Active infection.
- Other serious illness not controlled by adequate treatment.
- Inadequate organ function including:
- Absolute neutrophils counts<1.5 x 10^9/L
- Platelets counts<100 x 10^9/L
- Hemoglobin<9.0 g/dL (without red blood cells transfusion during 28 days prior to the test)
- Calculated creatinin clearance<60 ml/min
- Total bilirubin > or = 1.5 mg/dL
- Alanine aminotransferase/aspartate aminotransferase>1.5 times the upper normal limits of the institutional norms.
- Alkaline phosphatase (AP)>2.5 times the upper normal limits of the institutional norms. An increase of AP up to grade 2 would be accepted only if this increase is related to the presence of bone metastases. Bone specific isoenzyme AP should be greater than the pathological limit defined by the manufacturer as a sign of bone metastases.
- Documented medical history of myocardial infarction, documented angina pectoris, arrhythmia especially severe conduction disorder such as second or third degree atrio-ventricular block, stroke, or history of arterial or venous thrombo-embolism within the past 180 days requiring anticoagulants.
- Patient with a left ventricular ejection fraction<50% by echocardiography.
- Patient with a baseline QTc interval of >0.45, or family history of Long QT Syndrome
- Patient with uncontrolled hypertension and patient with organ damage related to hypertension such as left ventricular hypertrophy or grade 2 ocular funduscopic changes or kidney impairment.
- Patient with growing vessel disease (eg age-related macular degeneration, diabetic retinopathy, rheumatoid arthritis), or ongoing wound healing process. Patient should be enrolled in the study at least 28 days after surgery.
- 12-lead Electrocardiogram: ST- and T-wave changes suggesting ischemia
- Hypertension defined as systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg on two repeated measurements at 30 minutes intervals.
- Patient with one or more episodes of ventricular tachycardia with 3 or more consecutive premature beats, with a frequency > or = 180 beats/min.
Trial locations and contacts
2 sites in 1 country.
Japan2 sites
Sanofi-Aventis Investigational Site Number 392002
Osaka Sayama-Shi
Sanofi-Aventis Investigational Site Number 392001
Sunto-Gun
About this study
Official title: An Open-label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With AVE8062 Administered as a 30-minute Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.
Primary objective: To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of AVE8062 administered every 3 weeks in patients with advanced solid tumors.
Secondary objectives:
- To assess the overall safety profile of the drug.
- To characterize the pharmacokinetic profile of AVE8062 and its active metabolite RPR 258063.
- To evaluate anti-tumor activity of the drug.
Read the detailed description
The duration of the study for each patient will include an up to 4-week screening phase, 21-day study treatment cycles, an end of treatment visit and a follow-up period.
- Conditions
- Solid Tumor
- Being tested
- ombrabulin (AVE8062)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ombrabulin (AVE8062)Drug
Pharmaceutical form: injection solution
Route of administration: intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Level 1:
15.5 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal
Level 2:
25 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal
Level 3:
35 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal
Level 4:
50 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Receives: Drug: ombrabulin (AVE8062) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity at Cycle 1
Measured: 21 days
Secondary outcomes (4)
Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities
Measured: all cycles
Pharmacokinetic parameters of AVE8062: Cmax, AUC, CL, Vss, and t1/2
Measured: Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles
Pharmacokinetic parameters of AVE8062's active metabolite RPR258063: Cmax, AUC, t1/2, and Metabolic ratio
Measured: Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles
Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors in evaluable patients
Measured: from patient informed consent to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2009 (estimated)
- Study startSep 2009
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00968916
- Sponsor's protocol ID
- TED10967
- Status last verified
- Sep 2014
- First submitted
- 28 Aug 2009
- Last updated
- 19 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Murakami H, Kurata T, Onozawa Y, Watanabe J, Ono A, Takahashi T, Yamamoto N, Fujisaka Y, Kiyota H, Hayashi H, Tanaka K, Nakagawa K, Kuroda S. An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):623-30. doi: 10.1007/s00280-014-2388-x. Epub 2014 Jan 30.
PubMed 24477603
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With AVE8062 Administered as a 30-minute Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT00968916
- Acronym / sponsor ID
- TED10967
- Conditions
- Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Sep 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 31 Aug 2009 (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.
Primary objective: To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of AVE8062 administered every 3 weeks in patients with advanced solid tumors.
Secondary objectives:
- To assess the overall safety profile of the drug.
- To characterize the pharmacokinetic profile of AVE8062 and its active metabolite RPR 258063.
- To evaluate anti-tumor activity of the drug.
Detailed description
The duration of the study for each patient will include an up to 4-week screening phase, 21-day study treatment cycles, an end of treatment visit and a follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ombrabulin (AVE8062)Level 1: 15.5 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 2: 25 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 3: 35 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 4: 50 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Advanced solid tumor that has become refractory to conventional treatment or for which no standard therapy exists.
- Patients with signed and dated Institutional Review Board (IRB)-approved patient informed consent form (ICF) prior to enrollment in the study.
Key exclusion criteria (28 listed)
- Eastern Cooperative Oncology Group performance status > or = 2.
- Life expectancy of less than 12 weeks.
- Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study.
- Absence of histologically or cytologically proven cancer.
- Male patients who do not agree with contraception. Absence of negative serum/urinary pregnancy test within the 7 days prior to the enrollment in the study for female patients with childbearing potential. Patients must be post-menopausal, surgically sterile, or using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator).
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 |
|---|---|---|
| ombrabulin (AVE8062)Pharmaceutical form: injection solution Route of administration: intravenous infusion | Drug | 1 |
Primary outcome
Dose limiting toxicity at Cycle 1
Time frame: 21 days
4 secondary outcomes
Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities
Time frame: all cycles
Pharmacokinetic parameters of AVE8062: Cmax, AUC, CL, Vss, and t1/2
Time frame: Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles
Pharmacokinetic parameters of AVE8062's active metabolite RPR258063: Cmax, AUC, t1/2, and Metabolic ratio
Time frame: Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles
Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors in evaluable patients
Time frame: from patient informed consent to end of treatment
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 19 Sep 2014.
- Derived from this study: PubMed 24477603Murakami H, Kurata T, Onozawa Y, Watanabe J, Ono A, Takahashi T, Yamamoto N, Fujisaka Y, Kiyota H, Hayashi H, Tanaka K, Nakagawa K, Kuroda S. An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):623-30. doi: 10.1007/s00280-014-2388-x. Epub 2014 Jan 30.
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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.
Clinical Sciences & Operations study director
Sanofi
2 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 ombrabulin (AVE8062) in people with Solid Tumor, run by Sanofi at 2 sites in Japan.
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 2 inclusion and 28 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 19 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Japan. 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?
Dose limiting toxicity at Cycle 1 (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00968916, which also lists 1 linked publication.
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 19 Sep 2014.