Safety Study for Intravenous (IV) AC480 (AC480IV) to Treat Advanced Solid Tumors

NCT01245543 | Withdrawn Phase 1

• 1 other identifier: AC480IV-001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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.

  18 months

Secondary Outcomes (4)

• Determine the pharmacokinetic (PK) parameters (Cl, Vd, Cmax, Clast, AUClast, AUCinf, t1/2, etc.) of AC480IV and docetaxel as monotherapy and in combination.

  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.

  18 months

• Evaluate HER profile and Ras mutation status in patients' tumors

  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.

  Measured in specified dosing cohorts at various timepoints during Part 1 of this study.

Study Arms (2)

AC480IV

EXPERIMENTAL

Dose range finding study

Drug: Docetaxel

Docetaxel

EXPERIMENTAL

Dose range finding study in subjects with solid tumors

Drug: AC480IV

Interventions

AC480IV DRUG

AC480IV will be administered as an infusion using a dose escalation design.

Also known as: AC480IV•Esylate

Docetaxel

Docetaxel DRUG

Docetaxel will be administered intravenously, initially as monotherapy and subsequently in combination with docetaxel immediately following AC480IV administration.

Also known as: Taxol

AC480IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥18 years
• Provide written informed consent
• Has histological diagnosis of a primary solid tumor malignancy that meets study criteria
• Has measurable disease (or evaluable if not in MTD expansion cohort) via computed tomography (CT) or magnetic resonance imaging (MRI) scans with or without non-measurable tumors (a lesion in a previously irradiated area is eligible to be considered as measurable disease as long as there is objective evidence of progression of that lesion prior to enrollment)
• Less than 4 prior systemic cancer therapies (with the exception of hormonal agents), including experimental agents, prior HER-family TKI therapies, and prior docetaxel and other taxane therapy; there are no limits to the number of prior therapies for Part 1
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception.
• WOCBP must have a negative serum or urine pregnancy test (sensitivity ≤ 25IU human chorionic gonadotropin \[hCG\]/L) within 72 hours prior to the start of study drug administration
• Has an ECOG performance status of 0 or 1
• Has a life expectancy \>3 months
• Has adequate organ function as determined by laboratory tests

You may not qualify if:

• Patient is currently receiving or has received within the last month prior to Cycle 1 Day 1 (6 weeks for nitrosoureas, mitomycin-C, and liposomal doxorubicin) other chemotherapeutic, hormonal, or investigational anti-cancer agents with the exception of gonadal suppression agents and bisphosphonates for osteoporosis and skeletal metastases which may be continued while on study
• Patient has received other chemotherapeutic, hormonal, or investigational anti cancer agents that are outside of the timeframe described above and thus would be allowed in the study, but has toxicity that is unresolved (i.e., toxicity has resolved to Grade ≤ 1 or is deemed irreversible)
• Current or anticipated need for drugs that are known cytochrome P450 isozyme CYP3A4 or CYP2C8 inducers or inhibitors; only exception is oral glucocorticoids, which are a required premedication for docetaxel
• Patient received previous treatment with oral AC480
• Patient using herbal and dietary supplements that may interact with CYP3A4
• Patient received radiation therapy or major surgery within one month of Cycle 1 Day 1
• Patient has evidence of clinically unstable brain metastases (controlled and stable brain metastasis must be previously treated and asymptomatic)
• Patient has uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within 6 months prior to study entry;
• Uncontrolled angina within 6 months prior to study entry;
• History of congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4;
• LVEF that is ≤50% (or ≥ institutional lower limit of normal);
• Heart rate \<50 beats per minute;
• Diagnosed or suspected congenital long QT syndrome;
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes \[TdP\]);

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (2)

University of California San Francisco (UCSF)

San Francisco, California, 94118, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Interventions

Docetaxel; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Guy Gammon, MB BS, MRCP

  Interim Chief Medical Officer / Ambit Biosciences Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 22, 2010
• Study Start: November 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 2, 2015

Record last verified: 2015-10

Locations

US (2)