Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT02569489 |
Other study ID # |
HBI-8000-106 |
Secondary ID |
|
Status |
Withdrawn |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
December 2015 |
Est. completion date |
December 2015 |
Study information
Verified date |
June 2016 |
Source |
HUYABIO International, LLC. |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor
(HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with
advanced or metastatic HER2+ breast cancer.
Description:
This is a phase I multi-center dose escalation study of the histone deacetylase inhibitor
(HDACi) HBI-8000 when given in combination with paclitaxel and trastuzumab in women with
advanced or metastatic HER2+ breast cancer.
Three dose levels of HBI-8000 (15 mg, 20 mg, and 25 mg) will be tested using a standard 3+3
escalation plan with an expanded cohort at the maximum tolerated dose (MTD) to enroll a
minimum of 10 patients evaluable for safety to fulfill the requirements for moving the
combination forward to I-SPY 2 trial.
To be considered evaluable for safety, the patient must receive at least 75% of their
prescribed regimen per cycle for 4 consecutive cycles with a cycle of therapy defined as 28
days in the absence of disease progression or unacceptable toxicity. Patients who progress at
9 weeks evaluation or later but before completing 4 cycles and who have only experienced
Grade ≤ 1 toxicities (excluding alopecia) will also be considered evaluable for safety.
Enrolled patients will remain on their assigned dose level until unacceptable toxicity or
disease progression occurs. During dose escalation phase, if more than 34% of the evaluable
patients at a dose level experience dose limiting toxicities (DLT), this dose level will be
considered having exceeded MTD. Once MTD is identified during dose escalation phase, the MTD
dose level will be expanded in the expansion phase to enroll additional patients to ensure
that at least 10 patients are evaluable for safety at the MTD.
Paclitaxel and trastuzumab are administered by intravenous (IV) infusion on days 1, 8, 15,
and 22 of a 28-day cycle. HBI-8000 will be taken by mouth twice weekly at the assigned dose
on days 1, 4, 8, 11, 15, 18, 22 and 25 of a 28-day cycle. Treatment continues until disease
progression, unacceptable toxicity, or patient refusal/non-compliance is observed.
The study will evaluate the safety and tolerability of oral HBI-8000 bi-weekly in combination
with weekly paclitaxel and trastuzumab and if successful, determine an optimal dose to move
into phase II testing of this combination in the I-SPY 2 trial in a neo-adjuvant breast
cancer population.
To determine the MTD of HBI-8000 twice weekly in combination with weekly paclitaxel and
trastuzumab in women with HER2+ breast cancer.
- To determine the adverse event rate of twice weekly HBI-8000 in combination with weekly
paclitaxel and trastuzumab
- To determine the tolerability of twice weekly HBI-8000 when administered with weekly
paclitaxel and trastuzumab
- To explore efficacy of twice weekly HBI-8000 in combination with weekly paclitaxel and
trastuzumab
- To obtain pharmacokinetics of twice weekly HBI-8000 when administered in combination
with weekly paclitaxel and trastuzumab.
- To determine the on-target effect of HBI-8000 by measuring protein acetylation
- To explore the treatment effects on immune cells in blood and/or tumor tissue as
appropriate
Enrolled patients will take HBI-8000 at the assigned dose twice weekly while receiving weekly
paclitaxel and trastuzumab for a minimum of 8 weeks (2 treatment cycles). On the day of
paclitaxel infusion, HBI-8000 is taken at least one hour before paclitaxel infusion. HBI-8000
should be taken within 30 minutes after a meal. The interval between HBI-8000 administrations
is 3-4 days in the absence of dose delay or interruptions due to adverse events. For example,
three days should elapse between the 1st and 2nd dose of HBI-8000 of the week, such as
Monday/Thursday; Tuesday/Friday.
A disease re-evaluation will be scheduled every 8 weeks. Based on the Response Evaluation
Criteria in Solid Tumors 1.1 (RECIST1.1), response to treatment will be determined. Patients
with stable disease (SD), partial response (PR) or complete response (CR) may continue
treatment until disease progression, unacceptable side effects, or patient
refusal/non-compliance occurs.
Patients will be monitored in clinic every 4 weeks while receiving study treatment. The end
of treatment (EOT) visit will occur at 4 weeks after the last dose of HBI-8000, or before the
start of a new anti-cancer therapy, whichever is earlier. At EOT, patients will be evaluated
for resolution of treatment related toxicities. Toxicity related to HBI-8000, if not yet
resolved to Grade ≤ 1, will be followed until resolution to Grade ≤ 1 or considered chronic.
All patients will be followed up to 1 year from study enrollment for best objective response,
duration of response, time to PD, and survival.