Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01525602
Recruitment Status : Completed
First Posted : February 3, 2012
Results First Posted : July 16, 2020
Last Update Posted : July 16, 2020
Sponsor:
Collaborator:
Plexxikon
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This was a 3-part study designed to explore the safety and tolerability of escalating doses of PLX3397 with weekly paclitaxel to establish a recommended Phase 2 dose (RP2D), to confirm RP2D in participants with advanced non-resectable solid tumors, and to determine the efficacy of PLX3397 600 mg twice daily (BID) administered in combination with weekly paclitaxel in participants with advanced, metastatic or non-resectable, platinum-resistant or -refractory epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: PLX3397 Drug: Paclitaxel Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : May 2012
Actual Primary Completion Date : December 2017
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
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.

(Closed to recruitment)

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.

(Closed to recruitment)

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 combination 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.

(Closed to recruitment)

Drug: PLX3397
PLX3397 tablets, 200mg
Other Name: Pexidartinib

Drug: Paclitaxel
Paclitaxel IV
Other Name: Onxol




Primary Outcome Measures :
  1. Percentage of Participants With Treatment-emergent Adverse Events (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Safety Population) [ Time Frame: From post first dose up to 28 days after the last dose, up to 5 years 9 months ]
    Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Parts 1 and 2 are reported.

  2. Percentage of Participants With TEAEs (>10%) Classified by Preferred Term Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Safety Population) [ Time Frame: From post first dose up to 28 days after the last dose, up to 5 years 9 months ]
    Treatment-emergent adverse events (TEAEs) reported by >10% of all participants in Part 3 are reported.

  3. Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population) [ Time Frame: From post first dose up to 5 years 9 months post dose ]
    Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  4. Best Overall Tumor Response Based on RECIST V1.1 Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [ Time Frame: From 26 days (CR and PR) and 54 days (SD) up to 5 years 9 months post dose ]
    Best overall tumor response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) is reported, including participants who were not evaluable (NE). RECIST v1.1 for target lesions are assessed by magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography and are summarized as: CR, Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm; PR, At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; PD, at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (includes the baseline sum). In addition, the sum must also demonstrate an absolute increase of at least 5 mm; SD, Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.


Secondary Outcome Measures :
  1. Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Parts 1 and 2) (Efficacy Evaluable Population) [ Time Frame: From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose ]
  2. Duration of Response Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [ Time Frame: From the date of initial response until disease progression or death, whichever occurs first, up to 5 years 9 months post dose ]
  3. Progression-free Survival Following PLX3397 Administered in Combination With Paclitaxel (Part 3) (Efficacy Evaluable Population) [ Time Frame: From the first day of treatment to the first documented disease progression or date of death, whichever occurred first, up to 5 years 9 months post dose ]
    Progression-free survival (PFS) is defined as the number of days from the start of therapy (i.e. Cycle 1 Day 1) to the date of first documented disease progression/relapse or death, whichever occurs first. If the disease progression/relapse does not occur, PFS will be censored as of the date of their last evaluable tumor assessments.

  4. A Summary of Pharmacokinetic Parameter (Tmax) Following Exposure to PLX3397 (Parts 1 and 3) [ Time Frame: Cycle 1, Day 15 ]
  5. A Summary of Pharmacokinetic Parameter (Cmax) Following Exposure to PLX3397 (Parts 1 and 3) [ Time Frame: Cycle 1, Day 15 ]
  6. A Summary of Pharmacokinetic Parameters (AUC[0-4h], AUC[0-6h], and AUC[0-12h]) Following Exposure to PLX3397 (Parts 1 and 3) [ Time Frame: Cycle 1, Day 15 ]
  7. Percentage of Participants With PLX3397-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set) [ Time Frame: From post first dose up to 28 days after the last dose, up to 5 years 9 months ]
  8. Percentage of Participants With Paclitaxel-Related Treatment-emergent Adverse Events (>10%) by Preferred Term (Parts 1 and 2) (Safety Analysis Set) [ Time Frame: From post first dose up to 28 days after the last dose, up to 5 years 9 months ]
  9. Percentage of Participants With PLX3397- and/or Paclitaxel-Related TEAEs (>10%) by Preferred Term (Part 3) (Safety Analysis Set) [ Time Frame: From post first dose up to 28 days after the last dose, up to 5 years 9 months ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 (enrollment closed): 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 six months of Cycle 1 Day 1 (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 plasma half-life (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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2, inclusive
  • Anticipated life expectancy of at least 12 weeks
  • Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/mm3
  • Adequate renal function: serum creatinine <1.5 x ULN or calculated creatinine clearance (CrCl) >60 mL/min using Cockcroft-Gault formula
  • Adequate hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal (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 QT interval corrected by Fridericia's formula (QTcF) <450 ms (males) or <470 ms (females) on electrocardiogram (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01525602


Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Univeristy of California, San Francisco
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado, Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Florida
Sylvester Comprehensive Cancer Center/UMHC
Miami, Florida, United States, 33136
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Ohio State University
Columbus, Ohio, United States, 43210
United States, Utah
University of Utah, Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Plexxikon
  Study Documents (Full-Text)

Documents provided by Daiichi Sankyo, Inc.:
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT01525602    
Other Study ID Numbers: PLX108-07
First Posted: February 3, 2012    Key Record Dates
Results First Posted: July 16, 2020
Last Update Posted: July 16, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Keywords provided by Daiichi Sankyo, Inc.:
advanced, incurable solid tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action