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A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent and in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Solid Tumors, Untreated Pancreatic Adenocarcinoma, Pancreatic Cancer Non-resectable, Metastatic Pancreatic Adenocarcinoma

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Trial Information

A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent and in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Solid Tumors

Part 1 of the study is an open label, sequential PLX7486-TsOH single-agent dose escalation
in patients with solid tumors. This part of the study will include approximately 50 solid
tumor patients from 3-6 treatment sites. The starting dose will be 30 mg. Each treatment
cycle will be 21 days. Cohorts of 3 patients will be enrolled in a standard '3+3' design.
In the absence of drug-related Grade 2 toxicity, the dose escalation will occur in 100%
increments. The dose escalation will be reduced in increments of approximately 50% or less
if there is either a dose-limiting toxicity (DLT) or at least 2 patients in one cohort
experience ≥ Grade 2 toxicities that are considered possibly or probably related to PLX7486.
In part 1, the secondary objective is efficacy, as measured by overall response rate,
clinical benefit response rate, duration of response, and progression-free survival.
Exploratory endpoints will include changes in pain severity scores and analgesic consumption
and investigation of peripheral blood biomarkers and archival tumor tissue.

Part 2a of the study is also an open-label, sequential dose escalation of PLX7486-TsOH with
fixed dose levels of gemcitabine + nab-paclitaxel in patients with solid tumors.
Approximately 30 solid tumor patients will be enrolled using the standard '3+3' design.

Part 2b extension cohort is planned at the recommended phase 2 dose (RP2D) of PLX7486-TsOH
in combination with fixed dose levels of gemcitabine and nab-paclitaxel in 28-day treatment
cycles. Approximately 50 patients with previously untreated pancreatic adenocarcinoma will
be enrolled to ensure 38 patients (28 patients with metastatic disease and 10 patients with
locally advanced disease)will be evaluable for response.

In parts 2a and 2b, secondary endpoints include best overall response rate, duration of
response, clinical benefit response rate, and pharmacokinetics. Exploratory endpoints for
both parts 2a and 2b will include changes in pain severity scores and analgesic consumption,
and investigation of biomarker data in peripheral blood and archival tumor tissue.

Inclusion Criteria:

1. Male or female ≥18 years old

2. Patients with solid tumors who:

1. Part 1: have tumor progression following standard therapy, have
treatment-refractory disease, or for whom there is no effective standard of

2. Part 2a: have received ≤2 prior chemotherapy regimens for the treatment of their
primary malignancy and for whom gemcitabine and nab-paclitaxel would be
considered a reasonable chemotherapy option

3. Part 2b: have previously untreated locally advanced, non-resectable or
metastatic pancreatic adenocarcinoma, are not candidates for FOLFIRINOX
treatment(i.e., leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin.)
Patients who received prior neoadjuvant or adjuvant therapy with recurrent
disease ≥6 months following completion of the regimen are also eligible

3. Patients in Part 2b must have measurable disease by Response Evaluation Criteria for
Solid Tumors (i.e., RECIST) criteria v1.1

4. Women of child-bearing potential must have a negative pregnancy test within 7 days of
initiation of dosing and must agree to use an acceptable method of birth control from
the time of the negative pregnancy test up to 3 months after the last dose of study
drug. Women of non-childbearing potential may be included if they are either
surgically sterile or have been postmenopausal for ≥1 year. Fertile men must also
agree to use an acceptable method of birth control while on study drug and up to 3
months after the last dose of study drug.

5. All associated toxicity from previous or concurrent cancer therapy must be resolved
(to ≤ Grade 1 or Baseline) prior to study treatment administration.

6. Patients with stable, treated brain metastases are eligible for this trial. However,
patients must not have required steroid treatment for their brain metastases within
30 days of Screening.

7. Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements

8. Karnofsky performance score ≥ 70%

9. Life expectancy ≥3 months.

10. Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

1. Other than the primary malignancy, active cancer (either concurrent or within the
last 3 years) that requires non-surgical therapy (e.g. chemotherapy or radiation
therapy), with the exception of surgically treated basal or squamous cell carcinoma
of the skin, melanoma in-situ, or carcinoma in-situ of the cervix.

2. Chemotherapy within 28 days prior to Screening

3. Biological therapy within 5 half-lives of Screening

4. Radiation therapy within 14 days prior to Screening

5. Investigational drug use within 28 days or 5 half-lives, whichever is longer, prior
to Screening

6. Part 1 only: active or a history of glucose intolerance or diabetes mellitus

7. Part 2a and 2b only: known hypersensitivity to gemcitabine or nab-paclitaxel

8. Part 2a and 2b: uncontrolled diabetes. Patients with glucose intolerance or diabetes
whose blood glucose levels are consistently well-controlled with the use of oral
hypoglycemic agents and/or insulin are permitted.

9. Part 2b only: received radiotherapy, surgery, chemotherapy or investigational therapy
for the treatment of metastatic pancreatic adenocarcinoma. Prior treatment with
5-Fluorouracil or gemcitabine administered as a radiation sensitizer in the adjuvant
setting is allowed, provided at least 6 months have elapsed since last dose and no
lingering toxicities.

Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in
the adjuvant setting are not eligible for this study

10. Hemoglobin A1c >8%

11. ≥ Grade 2 sensory neuropathy at baseline

12. Uncontrolled intercurrent illness (i.e., active infection) or concurrent condition
that, in the opinion of the Investigator, would interfere with the study endpoints or
the patient's ability to participate

13. Refractory nausea and vomiting, malabsorption, small bowel resection that, in the
opinion of the Investigator, would preclude adequate absorption

14. Mean corrected QT interval (QTcF) ≥450 msec (for males) or ≥470 msec (for females) at

15. The presence of a medical or psychiatric condition that, in the opinion of the
Principal Investigator, makes the patient inappropriate for inclusion in this study

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of PLX7486 as single agent and in combination with gemcitabine and nab-paclitaxel

Outcome Description:

Adverse events, physical examinations, vital signs, clinical laboratory tests (hematology, chemistry, and urinalysis), ECGs, ophthalmic examinations, will all be evaluated to determine dose-limiting toxicities, i.e., any adverse event that is temporally related to the study drug administration and is not due to the patient's underlying malignancy and for which there is no clear evidence for an alternative etiology.

Outcome Time Frame:

Measured from baseline and weekly for the duration of drug administration, estimated to be ≤1 year.

Safety Issue:


Principal Investigator

Mai H Le, MD

Investigator Role:

Study Director

Investigator Affiliation:

Plexxikon Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

Related Keywords:

  • Solid Tumors
  • Untreated Pancreatic Adenocarcinoma
  • Pancreatic Cancer Non-resectable
  • Metastatic Pancreatic Adenocarcinoma
  • pancreatic adenocarcinoma
  • solid tumors
  • non-resectable pancreatic cancer
  • metastatic pancreatic cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms
  • Neoplasms



Sarah Cannon Research Institute (SCRI)Nashville, Tennessee  37203
Translational Genomics Research Institute (TGen)Scottsdale, Arizona  85258
University of California, Los Angeles Medical Center (UCLA)Santa Monica, California  90404
Medical Universtiy of South Carolina (MUSC)Charleston, South Carolina  29425