Solid TumorsPhase 1NCT00942799
Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Solid Tumors
A Phase 1 study testing Genz-644282 (28-day dosing schedule) and Genz-644282 (21-day dosing schedule) in people with Solid Tumors, run by Genzyme, a Sanofi Company at 4 sites in United States.
Trial summary
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an intravenous (IV) infusion, to patients with advanced malignant solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Genz-644282 (28-day dosing schedule) and Genz-644282 (21-day dosing schedule)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2009to Jan 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
- Signed written informed consent
- Patients enrolled in dose-escalation phase: Histologically or cytologically confirmed advanced malignant solid tumor for which no standard therapeutic option exists.
- For the disease indications evaluated in the expansion phase, the following criteria must be met:
- Have one of the following histologically or cytologically confirmed advanced malignant solid tumors for which no standard therapeutic option exists:
- Colorectal cancer (prior systemic regimen must have included ≥1 of the following: fluoropyrimidine or oxaliplatin);
- Squamous Non-small cell lung cancer or small cell lung cancer (prior systemic regimen must have included ≥1 of the following: cis-platinum or carbo platinum);
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- Pancreatic cancer (prior systemic regimen must have included gemcitabine);
- Breast cancer (prior systemic regimen must have included ≥1 of the following: taxane, anthracycline, or fluoropyrimidine)
- Received no more than 4 prior systemic therapy regimens for their malignancy
- Experienced progression or intolerance to their immediate prior systemic therapy regimen.
- Evaluable or measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Adequate organ and hematologic function.
- Prior chemotherapy, major surgery, or irradiation must have been completed at least 3 weeks prior to starting treatment with study drug, with the exception of mitomycin-C or nitrosoureas, which should be completed at least 6 weeks prior. Additionally, patients must have recovered to ≤ Grade 1 toxicities incurred as a result of the previous therapy, with the exception of nail dystrophy, alopecia, or local radiation therapy induced adverse events (e.g., impotence or incontinence). A patient who has received radiation to < 5% of their total bone marrow volume and who has had 2 weeks of rest may be considered for study entry after discussion with the Sponsor
- Hormone treatment must have been completed > 2 weeks prior to receiving study drug.
- Prostate cancer patients who are chemically castrated with hormonal therapy (e.g., luteinizing hormone-releasing hormone agonists) will be allowed to enter the study. However, doses and schedules of such treatments must be maintained throughout the trial and all major toxicities must have resolved to ≤ Grade 1 prior to study entry.
- Concomitant stable treatment with bisphosphonates is allowed, unless dose requires readjustments or discontinuation.
- Ability to comply with study procedures and follow-up examinations.
- Male and female patients must agree to use an effective barrier means of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) throughout the entire duration of the study and for at least 3 months after last dose of study drug.
- Male patients must agree to not donate sperm throughout the study and for at least 3 months following the last dose of study drug.
Who cannot join
- Received previous treatment with or have a known hypersensitivity to Genz-644282 or to any of its components.
- Received radiotherapy to the only site of measurable disease, unless the tumor at this site continues to increase in size after the patient has completed radiotherapy treatment.
- Used any investigational agent, other than anti-cancer chemotherapy, during the 4 weeks prior to the first dose of Genz-644282.
- Have psychiatric disorder(s) that would interfere with consent, study participation, or follow up (with the possible exception of incompetence as defined by New Jersey for the purposes of participation in clinical trials in the state of New Jersey).
- Have uncontrolled congestive heart failure or angina, a history of myocardial infarction within 6 months prior to study enrollment, or a cardiac functional capacity Class III or IV, as defined by the New York Heart Association Classification.
- Have a resting QT with Bazett's correction (QTcB) interval of > 460 msec, calculated as the average of at least 2 of the longest QT intervals measured on 12-lead recordings made prior to dosing with Genz-644282.
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- Have a systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics or other treatment.
- Have any other severe concurrent disease or a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo chemotherapy.
- A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) or viral hepatitis B or C.
- Presence of ≥ Grade 2 peripheral neuropathy.
- Pregnant or lactating women, due to the unknown effects of Genz-644282 on the developing fetus or newborn infant.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Wayne State University, Division of Hematology/Oncology, Karmanos Cancer Institute
Detroit, Michigan
Cancer Institute of New Jersey
New Brunswick, New Jersey
TGen Clinical Research Services at Scottsdale Healthcare
Scottsdale, Arizona
Moffitt Cancer Center
Tampa, Florida
About this study
Official title: A Phase I, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Advanced Malignant Solid Tumors
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an intravenous (IV) infusion, to patients with advanced malignant solid tumors. Each 28 day cycle of treatment will consist of 3 consecutive weeks of treatment every 28 days(i.e., treatment will be administered on Days 1, 8, and 15 every 28 days). Each 21 day cycle of treatment will consist of 2 consecutive weeks of treatment every 21 days(i.e., treatment will be administered on Days 1 and 8 every 21 days). Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Approximately 110 patients will be enrolled in this study. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) for the 2 dosing schedules are established. To further evaluate safety, approximately 40 additional patients with advanced malignant solid tumors will be enrolled and treated at the MTDs (20 for each dosing schedule) during an expansion phase.
Read the detailed description
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an IV infusion, to patients with advanced malignant solid tumors. Drug will be administered as a 60-minute IV infusion on days 1, 8, and 15 of the 28 day treatment cycle, or on days 1 and 8 of the 21 day treatment cycle.
Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) are established.
Safety will be evaluated throughout the study.
- Conditions
- Solid Tumors
- Being tested
- Genz-644282 (28-day dosing schedule), Genz-644282 (21-day dosing schedule)
- Keywords
- Genz-644282, Topoisomerase I inhibitors, Top1, solid tumors, dose-escalation, pharmacokinetic (PK), MTD (Maximum Tolerated Dose), oncology, cancer
- Medical subject headings
- Metatropic dwarfism, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genz-644282 (28-day dosing schedule)Drug
Genz-644282 will be administered as a 60-minute IV infusion. The initial dose of Genz-644282 will be 0.5 mg/m2 and will be administered once weekly for 3 consecutive weeks on Day 1, Day 8, and Day 15 of the 28 day cycle. Each 28-day period will represent one treatment cycle. Study drug will continue to be given until disease progression or unacceptable toxicity is observed.
Genz-644282 (21-day dosing schedule)Drug
The starting dose of Genz-644282 for the 21-day schedule will be prescriptive and will be based on review of available safety data from the 28-day dosing schedule by the Investigator and Sponsor. Patients will receive Genz-644282 once-weekly for 2 consecutive weeks on Day 1 and Day 8 of a 21 day cycle. Each 21-day period will represent 1 treatment cycle. Patients enrolled in subsequent cohorts will receive higher doses until the MTD is established.
| Study group | Role | What they receive |
|---|---|---|
| Study Drug: Genz-644282 (28-day dosing schedule) | Experimental | Genz-644282 (Each cohort will be based on dose-escalation) Receives: Drug: Genz-644282 (28-day dosing schedule) |
| Study Drug: Genz-644282 (21-day dosing schedule) | Experimental | Genz-644282 (Each cohort will be based on dose-escalation) Receives: Drug: Genz-644282 (21-day dosing schedule) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules
Measured: 24 Months
Secondary outcomes (8)
Determine the recommended Phase 2 doses for the 28-day and 21-day dosing schedules
Measured: 36 Months
Establish the pharmacokinetic (PK) profile through calculation of area under the curve of blood and urine concentrations.
Measured: 36 Months
Pharmacokinetics (PK) as measured by maximal observed concentration (Cmax)
Measured: 36 months
Pharmacokinetics (PK) as measured by time to maximal observed concentration (Tmax)
Measured: 36 months
Pharmacokinetics (PK) as measured by half-life (T1/2)
Measured: 36 months
Pharmacokinetics (PK) as measured by the amount and fraction of drug excreted in urine
Measured: 36 months
Assess evidence of antitumor activity
Measured: 36 months
Evaluate ongoing benefit as determined by the investigator and defined as an improvement in performance status
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00942799
- Sponsor's protocol ID
- GZ28200108
- Status last verified
- Mar 2014
- First submitted
- 17 Jul 2009
- Last updated
- 19 Mar 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Advanced Malignant Solid Tumors
- ClinicalTrials.gov ID
- NCT00942799
- Acronym / sponsor ID
- GZ28200108
- Conditions
- Solid Tumors
- Keywords
- Genz-644282, Topoisomerase I inhibitors, Top1, solid tumors, dose-escalation, pharmacokinetic (PK), MTD (Maximum Tolerated Dose), oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2009
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 21 Jul 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.
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an intravenous (IV) infusion, to patients with advanced malignant solid tumors. Each 28 day cycle of treatment will consist of 3 consecutive weeks of treatment every 28 days(i.e., treatment will be administered on Days 1, 8, and 15 every 28 days). Each 21 day cycle of treatment will consist of 2 consecutive weeks of treatment every 21 days(i.e., treatment will be administered on Days 1 and 8 every 21 days). Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Approximately 110 patients will be enrolled in this study. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) for the 2 dosing schedules are established. To further evaluate safety, approximately 40 additional patients with advanced malignant solid tumors will be enrolled and treated at the MTDs (20 for each dosing schedule) during an expansion phase.
Detailed description
This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the safety and tolerability of Genz-644282, administered as an IV infusion, to patients with advanced malignant solid tumors. Drug will be administered as a 60-minute IV infusion on days 1, 8, and 15 of the 28 day treatment cycle, or on days 1 and 8 of the 21 day treatment cycle.
Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity is observed. Patients will be enrolled in escalating dose cohorts until the Maximum Tolerated Doses (MTDs) are established.
Safety will be evaluated throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Drug: Genz-644282 (28-day dosing schedule) | Experimental | Drug: Genz-644282 (28-day dosing schedule)Genz-644282 (Each cohort will be based on dose-escalation) |
| Study Drug: Genz-644282 (21-day dosing schedule) | Experimental | Drug: Genz-644282 (21-day dosing schedule)Genz-644282 (Each cohort will be based on dose-escalation) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Signed written informed consent
- Patients enrolled in dose-escalation phase: Histologically or cytologically confirmed advanced malignant solid tumor for which no standard therapeutic option exists.
- For the disease indications evaluated in the expansion phase, the following criteria must be met:
- Evaluable or measurable disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (11 listed)
- Received previous treatment with or have a known hypersensitivity to Genz-644282 or to any of its components.
- Received radiotherapy to the only site of measurable disease, unless the tumor at this site continues to increase in size after the patient has completed radiotherapy treatment.
- Used any investigational agent, other than anti-cancer chemotherapy, during the 4 weeks prior to the first dose of Genz-644282.
- Have psychiatric disorder(s) that would interfere with consent, study participation, or follow up (with the possible exception of incompetence as defined by New Jersey for the purposes of participation in clinical trials in the state of New Jersey).
- Have uncontrolled congestive heart failure or angina, a history of myocardial infarction within 6 months prior to study enrollment, or a cardiac functional capacity Class III or IV, as defined by the New York Heart Association Classification.
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 |
|---|---|---|
| Genz-644282 (28-day dosing schedule)Genz-644282 will be administered as a 60-minute IV infusion. The initial dose of Genz-644282 will be 0.5 mg/m2 and will be administered once weekly for 3 consecutive weeks on Day 1, Day 8, and Day 15 of the 28 day cycle. Each 28-day period will represent one treatment cycle. Study drug will continue to be given until disease progression or unacceptable toxicity is observed. | Drug | Study Drug: Genz-644282 (28-day dosing schedule) |
| Genz-644282 (21-day dosing schedule)The starting dose of Genz-644282 for the 21-day schedule will be prescriptive and will be based on review of available safety data from the 28-day dosing schedule by the Investigator and Sponsor. Patients will receive Genz-644282 once-weekly for 2 consecutive weeks on Day 1 and Day 8 of a 21 day cycle. Each 21-day period will represent 1 treatment cycle. Patients enrolled in subsequent cohorts will receive higher doses until the MTD is established. | Drug | Study Drug: Genz-644282 (21-day dosing schedule) |
Primary outcome
Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules
Time frame: 24 Months
8 secondary outcomes
Determine the recommended Phase 2 doses for the 28-day and 21-day dosing schedules
Time frame: 36 Months
Establish the pharmacokinetic (PK) profile through calculation of area under the curve of blood and urine concentrations.
Time frame: 36 Months
Pharmacokinetics (PK) as measured by maximal observed concentration (Cmax)
Time frame: 36 months
Pharmacokinetics (PK) as measured by time to maximal observed concentration (Tmax)
Time frame: 36 months
Pharmacokinetics (PK) as measured by half-life (T1/2)
Time frame: 36 months
Pharmacokinetics (PK) as measured by the amount and fraction of drug excreted in urine
Time frame: 36 months
Assess evidence of antitumor activity
Time frame: 36 months
Evaluate ongoing benefit as determined by the investigator and defined as an improvement in performance status
Time frame: 36 months
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 Mar 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.
Medical Monitor study director
Genzyme, a Sanofi Company
4 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 Genz-644282 (28-day dosing schedule) and Genz-644282 (21-day dosing schedule) in people with Solid Tumors, run by Genzyme, a Sanofi Company at 4 sites in United States.
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 21 inclusion and 11 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 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules (time frame: 24 Months). 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 19 Mar 2014.