Neoplastic Disease Clinical Trial
Official title:
A Phase I Trial of ABI-011 Administered Weekly in Patients With Advanced Solid Tumors or Lymphomas
The primary objective of study CA601.2 is to determine the maximum tolerated dose (MTD) or
recommended phase 2 dose (RP2D) of ABI-011 when administered by intravenous (IV) infusion on
Days 1, 8, and 15, followed by a week of rest, in patients with advanced solid tumor
malignancies or lymphomas. The MTD will be determined using a standard 3+3 design. The
secondary objectives are to evaluate the safety and toxicity profile, to evaluate the plasma
pharmacokinetics (PK), to assess the biological activity and pharmacodynamics, and to make a
preliminary assessment of tumor response in patients with advanced solid tumors or lymphomas.
The exploratory objectives are to determine the genomic and proteomic profile of patients'
tumors to identify gene mutations, gene amplifications, levels of protein expression, and
pinpoint oncoproteins. Correlations between genomic/proteomic profiles and efficacy outcomes
will be assessed and principal metabolites of ABI-011 will be determined, if possible.
Approximately 45-60 patients will be treated to determine dose limiting toxicities (DLTs),
the MTD, and/or RP2D of ABI-011. Once the RP2D is identified, expansion of this cohort (up to
10 patients) will occur.
ABI-011 is a novel, albumin-bound formulation of a potent thiocolchicine analog, IDN 5404,
with a mean particle size of approximately 100 nanometers (nm). The active drug, IDN 5404, is
related to the colchicine family of tubulin-binding compounds that have been found to have
vascular-disrupting activity in vivo. Studies are ongoing to determine whether IDN 5404 has
vascular-disrupting activity. As a dimer, IDN 5404 has an additional activity as an inhibitor
of topoisomerase I, a critical enzyme in deoxyribonucleic acid (DNA) repair mechanisms.
Although the active compound has limited solubility, IDN 5404 formulated as ABI-011 is
soluble in saline, facilitating IV dosing and delivery of the active agent to tumors and the
tumor vasculature.
The primary objective of study CA601.2 is to determine the MTD or RP2D of ABI-011 when
administered by IV infusion on Days 1, 8, and 15, followed by a week of rest, in patients
with advanced solid tumor malignancies or lymphomas. The MTD will be determined using a
standard 3+3 design. The secondary objectives are to evaluate the safety and toxicity
profile, to evaluate the plasma PK (elimination rate constant, elimination half-life, volume
of distribution, maximum serum concentration (Cmax), time to maximum concentration (tmax),
and area under the time-concentration curve to time infinity (AUCinf), to assess the
biological activity and pharmacodynamics, and to make a preliminary assessment of tumor
response in patients with advanced solid tumors or lymphomas. The exploratory objectives are
to determine the genomic and proteomic profile of patients' tumors to identify gene
mutations, gene amplifications, levels of protein expression, and pinpoint oncoproteins.
Correlations between genomic/proteomic profiles and efficacy outcomes will be assessed and
principal metabolites of ABI-011 will be determined, if possible.
Approximately 45-60 patients will be treated to determine DLTs, the MTD, and/or RP2D of
ABI-011. Once the RP2D is identified, expansion of this cohort (up to 10 patients) will
occur.
Patients with cytologically or histologically confirmed solid tumor malignancies or lymphoma
for which no curative standard approved therapy is available with an Eastern Cooperative
Oncology Group (ECOG) performance status ≤ 2 will be included. In the dose-escalation phase
of the study, patients can have measurable or non-measurable disease as defined by Response
Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, criteria. In the dose-expansion
phase of the study, only patients with measurable disease will be enrolled. No anti-cancer
therapies (inclusive of investigational therapies) are allowed 5 half-lives/4 weeks
(whichever is longer) prior to study drug administration (6 weeks for nitrosoureas or
mitomycin C).
ABI-011 will be administered via IV infusion for 30 minutes weekly on Days 1, 8, and 15 of a
28-Day cycle. The starting dose will be 2 mg/m2. Patients will be allowed to continue
treatment until they experience progressive disease or unacceptable toxicity, withdraw
consent, or their physician feels it is no longer in their best interest to continue on
treatment.
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