Safety Study of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Plexxikon
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01525602
First received: January 31, 2012
Last updated: August 8, 2016
Last verified: August 2016
  Purpose
The goal of this clinical study is to learn how PLX3397 and paclitaxel work together to affect the growth of cancer cells in advanced solid tumors.

Condition Intervention Phase
Solid Tumors
Drug: PLX3397
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study to Assess the Safety of PLX3397 and Paclitaxel in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Safety--Subject incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Safety of PLX3397 in combination with paclitaxel will be assessed by reported adverse events; and the results of physical examinations, vital signs, ECGs, hematology and serum chemistry laboratory values.


Secondary Outcome Measures:
  • Response to treatment according to RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: May 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1
Open-label, sequential PLX3397 single-agent dose escalation in combination with paclitaxel in approximately 30 patients with advanced solid tumors. Enrollment completed.
Drug: PLX3397
PLX3397 tablets, 200mg
Other Name: Pexidartinib
Drug: Paclitaxel
Paclitaxel IV
Other Name: Onxol
Experimental: Part 2
Extension cohort at the RP2D of single-agent PLX3397 in combination with paclitaxel in approximately 30 patients in advanced solid tumors. Enrollment completed.
Drug: PLX3397
PLX3397 tablets, 200mg
Other Name: Pexidartinib
Drug: Paclitaxel
Paclitaxel IV
Other Name: Onxol
Experimental: Part 3
Extension cohort at the RP2D of single-agent PLX3397 in combinator with paclitaxel in approximately 30 patients with advanced, metastatic, or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
Drug: PLX3397
PLX3397 tablets, 200mg
Other Name: Pexidartinib
Drug: Paclitaxel
Paclitaxel IV
Other Name: Onxol

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with:

    • Part 1 (enrollment closed): an advanced, incurable solid tumor
    • Part 2 (enrollment closed): an advanced, incurable solid tumor for whom a taxane would be considered a reasonable chemotherapy option
    • Part 3: advanced, metastatic or non-resectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer with

      • platinum-resistant cancer, defined as disease that responded to a platinum-containing chemotherapy regimen, but demonstrated recurrence within six months following the completion of that platinum-containing regimen, OR
      • platinum-refractory cancer, defined as disease failed to achieve at least a partial response to a platinum-containing regimen (i.e., stable disease or actual disease progression), AND
      • have not been treated with a taxane within one year of C1D1, AND
      • have not been treated with weekly paclitaxel after first-line treatment in which weekly paclitaxel plus a platinum is permitted
  • Part 3: Patients must have target (≥2 cm diameter) or non-target lesion cancer that is accessible for core biopsies before starting on study and after one cycle of treatment.
  • Patients with stable brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within 30 days of Screening.
  • Bone-directed therapy (e.g., bisphosphonates or denosumab) is permitted.
  • Washout from any prior investigational therapy of at least five times the T1/2 prior to C1D1
  • Washout from any prior biologic or targeted therapy at least 4 weeks or five times the T1/2 (whichever is shorter) prior to C1D1
  • Washout from prior chemotherapy of at least 2 weeks or 1 elimination half-life, whichever is longer, prior to C1D1
  • Washout from prior hormonal therapy of at least 2 weeks prior to C1D1
  • Washout of at least 2 weeks from the most recent radiation treatment prior to C1D1
  • Resolution of all prior treatment-related toxicities to Grade 1 or less, except for Grade 2 fatigue or alopecia prior to C1D1
  • Age eighteen years or older
  • ECOG performance status 0-2, inclusive
  • Anticipated life expectancy of at least 12 weeks
  • Adequate bone marrow reserve: ANC ≥1500/mm3, platelets ≥100,000/mm3
  • Adequate renal function: serum creatinine <1.5 x ULN or calculated CrCl >60 mL/min using Cockcroft-Gault formula
  • Adequate hepatic function: AST and ALT <2.5 x ULN, Total and Direct Bilirubin <1.5 x ULN. However, in the presence of liver metastases, AST and ALT must be <5 x ULN
  • Cardiac ejection fraction ≥50%, and QTcF<450 ms (males) or <470 ms (females) on ECG at Baseline.
  • Able to swallow capsules and maintain adequate hydration
  • Ability to give written informed consent and willing to comply with the requirements of the protocol; and for Part 3, to give written informed consent for 2 cancer biopsy procedures
  • Women of child-bearing potential must agree to use an effective method of birth control during treatment and for three months after receiving their last dose of study drug. Fertile men must also agree to use an acceptable method of birth control while on study drug and for at least 3 months after last dose.

Exclusion Criteria:

  • Presence of an active secondary malignancy.

    • Patients with a non-melanomatous, in situ malignancy or disease that is completely resectable with surgery may be considered after discussion with the Medical Monitor
    • Patients with a completely treated prior malignancy with no evidence of disease for ≥3 years are eligible
  • Refractory nausea and vomiting, malabsorption, external biliary shunt or significant small bowel resection that would preclude adequate absorption of PLX3397
  • Ongoing treatment with any other investigational therapy
  • Prior anaphylactic or severe hypersensitivity reaction to paclitaxel or Cremophor-containing agent.
  • Persistent grade 2 fatigue at Baseline.
  • Severe, concurrent illness including congestive heart failure, significant cardiac disease and uncontrolled hypertension, that would likely prevent the patient from being able to comply with the study protocol
  • Active untreated infection
  • Known chronic active Hepatitis B or C, or HIV infection
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01525602

Contacts
Contact: Michael Pelayo mpelayo@plexxikon.com

Locations
United States, Alabama
Plexxikon Investigative Site Recruiting
Birmingham, Alabama, United States, 35233
United States, California
Plexxikon Investigative Site Recruiting
San Francisco, California, United States, 94143
United States, Colorado
Plexxikon Investigative Site Not yet recruiting
Denver, Colorado, United States, 80202
United States, Florida
Plexxikon Investigative Site Recruiting
Miami, Florida, United States, 33136
United States, Minnesota
Plexxikon Investigative Site Recruiting
Rochester, Minnesota, United States, 55905
United States, Ohio
Plexxikon Investigative Site Recruiting
Cleveland, Ohio, United States, 44106
Plexxikon Investigative Site Recruiting
Columbus, Ohio, United States, 43210
United States, Utah
Plexxikon Investigative Site Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Plexxikon
  More Information

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT01525602     History of Changes
Other Study ID Numbers: PLX108-07 
Study First Received: January 31, 2012
Last Updated: August 8, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Plexxikon:
advanced, incurable solid tumors

Additional relevant MeSH terms:
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 23, 2016