CancerPhase 1NCT00724100
A Trial of ALB 109564(a) in Subjects With Advanced Solid Tumors
A Phase 1 study testing ALB 109564(a) (12´-methylthiovinblastine dihydrochloride) in people with Cancer, run by Albany Molecular Research, Inc. at 2 sites in United States.
Trial summary
The purpose of this study is to determine the maximum tolerated dose of ALB 109564(a), a novel tubulin inhibitor, and to assess safety, pharmacokinetics, and anti-tumor activity in subjects with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- ALB 109564(a) (12´-methylthiovinblastine dihydrochloride)
- Type of treatment
- Injection or infusion
- How many people
- 46 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2008to Dec 2010
- 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
- Age ≥ 18 years of age.
- Histologically or cytologically confirmed solid tumor that is metastatic or progressive and for whom no standard therapy holds curative potential.
- Evaluable disease, measurable by either imaging using Response Evaluation Criteria in Solid Tumors (RECIST) or tumor marker(s).
- ECOG Performance Status of ≤ 2.
- Life expectancy of > 12 weeks.
- Laboratory values:
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- Absolute neutrophil count ≥ 1,500 cells/μL.
- Platelets ≥ 100,000 cells/μL.
- Total bilirubin ≤ 1.5 × ULN.
- AST (SGOT) ≤ 2.5 × ULN.
- ALT (SGPT) ≤ 2.5 × ULN.
- Serum creatinine ≤ 1.5 mg/dL, or a measured creatinine clearance of ≥ 50 mL/min.
- Subjects with primary liver cancer or hepatic metastasis are eligible, if the following criteria are met:
- Total bilirubin ≤ 1.5 mg/dL.
- AST (SGOT) and ALT (SGPT) ≤ 5 × ULN.
- Severe liver dysfunction (Child-Pugh Class C or uncompensated Class B with persistent encephalopathy, persistent ascites, prothrombin time > 1.5 × ULN) is not present.
- Ascites, if present, is managed with diuretic agents or repeated paracentesis (required no more frequently than once per month).
- Esophageal bleeding and varices, if present, have been sclerosed or banded, and no bleeding episodes have occurred during the prior 6 months.
- Subjects with asymptomatic treated brain metastasis (surgical resection or radiotherapy) are eligible, if neurologically stable and have been off steroids and anticonvulsants required for symptom control for at least 3 months before Cycle 1, Day 1.
Who cannot join
- Women who are pregnant or lactating or of child-bearing potential, but not using adequate contraception.
- Receipt of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before starting ALB 109564(a).
- Presence of acute or chronic adverse toxicity due to prior chemotherapy that has not resolved to ≤ Grade 1, as determined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0.
- Major surgery within 4 weeks before starting ALB 109564(a).
- Peripheral neuropathy of Grade ≥ 2 by CTCAE v3.0.
- Evidence of autonomic or other neuropathic syndromes, including chronic constipation.
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- Confirmed diagnosis of HIV.
- Active, uncontrolled infection or systemic inflammatory disease.
- Active hepatitis B or C or other active liver disease (other than malignancy).
- Contraindication to a vinca alkaloid.
- Use of any investigational agent within 4 weeks of starting ALB 109564(a).
- Uncontrolled intercurrent illness that would jeopardize the subject's safety, interfere with the objectives of the protocol, or limit the subject's compliance with study requirements, as determined by the Investigator in consultation with the Sponsor.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Montefiore-Einstein Cancer Center
The Bronx, New York, 10461
About this study
Official title: A Phase 1, Dose Escalation Study of the Safety and Pharmacokinetics of ALB 109564(a) Administered Intravenously Every 3 Weeks to Subjects With Advanced Solid Tumors
The purpose of this study is to determine the maximum tolerated dose of ALB 109564(a), a novel tubulin inhibitor, and to assess safety, pharmacokinetics, and anti-tumor activity in subjects with advanced solid tumors.
Read the detailed description
This is the first clinical study of ALB 109564(a), a tubulin inhibitor, interfering with tubulin polymerization, primarily targeting microtubules that compose the mitotic spindle, resulting in metaphase arrest. The motivation for the development of ALB 109564(a) is to create a molecule that will provide greater anti-tumor activity than other licensed vinca alkaloids, without increasing the level of toxicity often associated with such therapies.
The objectives of the proposed study are: (1) to determine the safety and tolerability, including the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), of ALB 109564(a) administered intravenously every 3 weeks to subjects with advanced, treatment-refractory solid tumors; (2) to evaluate the pharmacokinetics of ALB 109564(a); and (3) to document any observed anti-tumor activity.
The starting dose of 1.2 mg/m2 once every 3 weeks is expected to ensure a safe first-in-human dose and allow increases of 50% with the first several subject cohorts. The first cohort will enroll 3 subjects, and the subsequent 3-subject cohorts will proceed according to a modified Fibonacci scheme. The standard dose increase, in the absence of dose limiting toxicity, will be 50%. However, once 1 subject experiences a DLT, or 2 or more subjects within a cohort experience ≥ Grade 2 drug-related adverse events, all subsequent dose escalations will occur at approximately 25% increments. In the case that the dose escalation increment is decreased to 25% following 2 or more subjects with ≥ Grade 2 drug-related events, the increment can subsequently be reset at 50% if, in the 2 successive cohorts, no DLTs are observed, and no more than 1 subject per cohort experiences a ≥ Grade 2 drug-related AE. DLT and MTD determinations will be made according to the first treatment cycle (single dose plus 3-week follow-up). The MTD will be declared as the highest level at which none of the original 3 subjects or no more than 1 of the expanded 6-subject cohort experiences a DLT. At the MTD level, subjects will be enrolled into two parallel groups: Group A, those with solid tumor of unrestricted tumor type, and Group B, those with primary tumor type of soft tissue sarcoma. Up to a total of 24 subjects will be enrolled at the MTD.
Subjects who tolerate treatment will be eligible to continue receiving treatment to a maximum of 12 cycles on the same 3-week schedule per the Investigator's medical judgment. Subjects whose disease has not progressed after 12 cycles of treatment with ALB 109564(a) may continue receiving treatment on the same 3-week cycle, with the same protocol assessments, contingent upon the Investigator's judgment and the Sponsor's approval.
The actual enrollment of subjects will be determined by the safety experience and the number of dose-escalation cohorts required to achieve the MTD. The projected enrollment is approximately 60 subjects for a total study duration of approximately 2 years.
- Conditions
- Cancer
- Being tested
- ALB 109564(a) (12´-methylthiovinblastine dihydrochloride)
- Keywords
- Malignancy, Solid tumor, Tubulin inhibitor
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALB 109564(a) (12´-methylthiovinblastine dihydrochloride)Drug
Starting dose is 1.2 mg/m2. Standard dose increase, in the absence of limiting toxicity, is 50%. Each dose of ALB 109564(a) will be administered by intravenous infusion once every 3 weeks (21-day cycle) over a period of time up to approximately 30 minutes. Number of cycles: Maximum of 12, until disease progression, or unacceptable toxicity develops. Greater than 12 cycles if disease has not progressed after 12 cycles, with Investigator's and Sponsor's approvals.
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose and dose limiting toxicity.
Measured: Every treatment cycle
Secondary outcomes (1)
Anti-tumor activity (objective tumor response, time to progression, duration of response)
Measured: Following every even-numbered cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2010
- Study completionDec 2010
Why it stopped: Sponsor's decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albany Molecular Research, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Westat
- Responsible party
- Sponsor
- Investigators
- Daniel Cho, MD, Principal investigator, Beth Israel Deaconess Medical CenterGeoffrey Shapiro, MD, PhD, Principal investigator, Dana-Farber Cancer InstituteEunice L. Kwak, MD, PhD, Principal investigator, Massachusetts General HospitalSridhar Mani, MD, Principal investigator, Montefiore-Einstein Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00724100
- Sponsor's protocol ID
- AMRI-564-101
- Status last verified
- Sep 2011
- First submitted
- 25 Jul 2008
- Last updated
- 27 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose Escalation Study of the Safety and Pharmacokinetics of ALB 109564(a) Administered Intravenously Every 3 Weeks to Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00724100
- Acronym / sponsor ID
- AMRI-564-101
- Conditions
- Cancer
- Keywords
- Malignancy, Solid tumor, Tubulin inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Albany Molecular Research, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Westat
- Study start
- Sep 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 29 Jul 2008 (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 determine the maximum tolerated dose of ALB 109564(a), a novel tubulin inhibitor, and to assess safety, pharmacokinetics, and anti-tumor activity in subjects with advanced solid tumors.
Detailed description
This is the first clinical study of ALB 109564(a), a tubulin inhibitor, interfering with tubulin polymerization, primarily targeting microtubules that compose the mitotic spindle, resulting in metaphase arrest. The motivation for the development of ALB 109564(a) is to create a molecule that will provide greater anti-tumor activity than other licensed vinca alkaloids, without increasing the level of toxicity often associated with such therapies.
The objectives of the proposed study are: (1) to determine the safety and tolerability, including the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), of ALB 109564(a) administered intravenously every 3 weeks to subjects with advanced, treatment-refractory solid tumors; (2) to evaluate the pharmacokinetics of ALB 109564(a); and (3) to document any observed anti-tumor activity.
The starting dose of 1.2 mg/m2 once every 3 weeks is expected to ensure a safe first-in-human dose and allow increases of 50% with the first several subject cohorts. The first cohort will enroll 3 subjects, and the subsequent 3-subject cohorts will proceed according to a modified Fibonacci scheme. The standard dose increase, in the absence of dose limiting toxicity, will be 50%. However, once 1 subject experiences a DLT, or 2 or more subjects within a cohort experience ≥ Grade 2 drug-related adverse events, all subsequent dose escalations will occur at approximately 25% increments. In the case that the dose escalation increment is decreased to 25% following 2 or more subjects with ≥ Grade 2 drug-related events, the increment can subsequently be reset at 50% if, in the 2 successive cohorts, no DLTs are observed, and no more than 1 subject per cohort experiences a ≥ Grade 2 drug-related AE. DLT and MTD determinations will be made according to the first treatment cycle (single dose plus 3-week follow-up). The MTD will be declared as the highest level at which none of the original 3 subjects or no more than 1 of the expanded 6-subject cohort experiences a DLT. At the MTD level, subjects will be enrolled into two parallel groups: Group A, those with solid tumor of unrestricted tumor type, and Group B, those with primary tumor type of soft tissue sarcoma. Up to a total of 24 subjects will be enrolled at the MTD.
Subjects who tolerate treatment will be eligible to continue receiving treatment to a maximum of 12 cycles on the same 3-week schedule per the Investigator's medical judgment. Subjects whose disease has not progressed after 12 cycles of treatment with ALB 109564(a) may continue receiving treatment on the same 3-week cycle, with the same protocol assessments, contingent upon the Investigator's judgment and the Sponsor's approval.
The actual enrollment of subjects will be determined by the safety experience and the number of dose-escalation cohorts required to achieve the MTD. The projected enrollment is approximately 60 subjects for a total study duration of approximately 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age ≥ 18 years of age.
- Histologically or cytologically confirmed solid tumor that is metastatic or progressive and for whom no standard therapy holds curative potential.
- Evaluable disease, measurable by either imaging using Response Evaluation Criteria in Solid Tumors (RECIST) or tumor marker(s).
- ECOG Performance Status of ≤ 2.
- Life expectancy of > 12 weeks.
Key exclusion criteria (12 listed)
- Women who are pregnant or lactating or of child-bearing potential, but not using adequate contraception.
- Receipt of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before starting ALB 109564(a).
- Presence of acute or chronic adverse toxicity due to prior chemotherapy that has not resolved to ≤ Grade 1, as determined using the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0.
- Major surgery within 4 weeks before starting ALB 109564(a).
- Peripheral neuropathy of Grade ≥ 2 by CTCAE v3.0.
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 |
|---|---|---|
| ALB 109564(a) (12´-methylthiovinblastine dihydrochloride)Starting dose is 1.2 mg/m2. Standard dose increase, in the absence of limiting toxicity, is 50%. Each dose of ALB 109564(a) will be administered by intravenous infusion once every 3 weeks (21-day cycle) over a period of time up to approximately 30 minutes. Number of cycles: Maximum of 12, until disease progression, or unacceptable toxicity develops. Greater than 12 cycles if disease has not progressed after 12 cycles, with Investigator's and Sponsor's approvals. | Drug | – |
Primary outcome
Maximum tolerated dose and dose limiting toxicity.
Time frame: Every treatment cycle
1 secondary outcome
Anti-tumor activity (objective tumor response, time to progression, duration of response)
Time frame: Following every even-numbered cycle
Results and safety
The study was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 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.
Daniel Cho, MD principal investigator
Beth Israel Deaconess Medical Center
Geoffrey Shapiro, MD, PhD principal investigator
Dana-Farber Cancer Institute
Eunice L. Kwak, MD, PhD principal investigator
Massachusetts General Hospital
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 ALB 109564(a) (12´-methylthiovinblastine dihydrochloride) in people with Cancer, run by Albany Molecular Research, Inc. at 2 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 19 inclusion and 12 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: stopped early, as of the sponsor's last update on 27 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 2 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 was stopped early (reason given: Sponsor's decision). Results are not available in the source record.
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?
Maximum tolerated dose and dose limiting toxicity. (time frame: Every treatment cycle). 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 27 Aug 2014.