- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00724100
A Trial of ALB 109564(a) in Subjects With Advanced Solid Tumors
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
-
-
New York
-
Bronx, New York, United States, 10461
- Montefiore-Einstein Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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:
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximum tolerated dose and dose limiting toxicity.
Time Frame: Every treatment cycle
|
Every treatment cycle
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Anti-tumor activity (objective tumor response, time to progression, duration of response)
Time Frame: Following every even-numbered cycle
|
Following every even-numbered cycle
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
- Principal Investigator: Daniel Cho, MD, Beth Israel Deaconess Medical Center
- Principal Investigator: Eunice L. Kwak, MD, PhD, Massachusetts General Hospital
- Principal Investigator: Sridhar Mani, MD, Montefiore-Einstein Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- AMRI-564-101
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer
-
Cellworks Group Inc.RecruitingCancer | Relapsed Cancer | Refractory CancerUnited States
-
University of Michigan Rogel Cancer CenterRecruitingCancer Liver | Cancer Brain | Cancer Head &Neck | Cancer PelvisUnited States
-
UNC Lineberger Comprehensive Cancer CenterHyundai Hope On WheelsRecruitingCancer | Pediatric Cancer | Survivorship | Cancer MetastaticUnited States
-
Vanderbilt-Ingram Cancer CenterNational Institutes of Health (NIH)Active, not recruitingAdvanced Cancer | Relapsed Cancer | Refractory CancerUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage III Pancreatic Cancer | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage IV Gastric Cancer | Stage IVA Colorectal Cancer | Stage IVA Pancreatic Cancer | Stage IVB Colorectal Cancer | Stage IVB Pancreatic Cancer | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric... and other conditionsUnited States
-
MiRXES Pte LtdRecruitingBreast Cancer | Gastric Cancer | Colorectal Cancer | Pancreatic Cancer | Esophageal Cancer | Ovarian Cancer | Prostate Cancer | Thoracic Cancer | Liver CancerSingapore
-
University of California, San FranciscoBristol-Myers Squibb; PfizerTerminatedStage IIIA Rectal Cancer | Stage IIIB Rectal Cancer | Stage IIIC Rectal Cancer | Metastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Rectal Adenocarcinoma | Stage IIIA Colon Cancer | Stage IIIB Colon Cancer | Stage IIIC Colon Cancer | Stage IV Colon Cancer | Stage IV Rectal... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
-
Massachusetts General HospitalNational Comprehensive Cancer NetworkCompletedGastric Cancer | Pancreatic Cancer | Esophageal Cancer | Rectal Cancer | Colon Cancer | Hepatobiliary CancerUnited States
-
Johns Hopkins UniversityNational Cancer Institute (NCI); National Institute on Minority Health and...Enrolling by invitationCancer | Advanced Cancer | End Stage Cancer | MalignancyUnited States