AC480IV will be administered as a monotherapy and then in combination with docetaxel in patients with locally advanced or metastatic solid tumors for whom there are no standard or curative therapies available. It is designed to evaluate the safety and pharmacokinetic parameters of AC480IV as monotherapy and also in combination with docetaxel under the conditions of the study.
A Phase I study to determine safety and tolerability of AC480IV with and without Docetaxel in subjects with solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
University of California San Francisco (UCSF)
San Francisco, California, United States
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, United States
Determine the safety and tolerability, including the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD), of a 2-day pulse of AC480IV both as monotherapy and in combination with docetaxel in patients with advanced solid tumor malignancies.
The primary outcome of the study will be safety and tolerability of the study treatment as measured by physical examinations, adverse events, clinical chemistry evaluations, ECG assessments and the report of dose-limiting toxicity as outlined in the protocol.
Time frame: 18 months
Determine the pharmacokinetic (PK) parameters (Cl, Vd, Cmax, Clast, AUClast, AUCinf, t1/2, etc.) of AC480IV and docetaxel as monotherapy and in combination.
This study is designed to evaluate the safety and PK parameters of AC480IV as monotherapy and also in combination with docetaxel.
Time frame: Measured at specified timepoints during 1st and/or 2nd cycles of treatment.
Determine any preliminary evidence of efficacy of AC480IV as monotherapy or in combination with docetaxel by assessing tumor response and time to disease progression.
Efficacy assessments will be completed within 7 days after the end of Cycle 3 and then every 3 cycles thereafter. Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) will be used to assess radiographic response.
Time frame: 18 months
Evaluate HER profile and Ras mutation status in patients' tumors
If possible, patients with tumors known to express HER receptors, such as head and neck, lung adenocarcinoma, upper GI/esophageal, and breast cancers will be included.
Time frame: Measured in specified dosing cohorts at various timepoints during 1st and/or 2nd cycles of treatment.
Evaluate whether AC480IV has anti-metabolic activity in the tumor microenvironment.
Tumor metabolism will be assessed by comparing pre-dose and postdose assessments.
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Time frame: Measured in specified dosing cohorts at various timepoints during Part 1 of this study.