Trial record 1 of 1 for:    plx7486
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Phase 1 Study of PLX7486 as Single Agent and With Gemcitabine Plus Nab-Paclitaxel in Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Plexxikon
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01804530
First received: March 1, 2013
Last updated: June 7, 2016
Last verified: June 2016

March 1, 2013
June 7, 2016
August 2013
February 2021   (final data collection date for primary outcome measure)
  • Safety of PLX7486 as single agent and in combination with gemcitabine and nab-paclitaxel as measured by adverse events and serious adverse events. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] will be used to assess the pharmacokinetic profile of PLX7486.
  • Peak concentration (Cmax) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.
  • Time to peak concentration (Tmax) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.
  • Half life (t1/2) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.
  • Terminal elimination rate constant (Kel) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.
Safety of PLX7486 as single agent and in combination with gemcitabine and nab-paclitaxel [ Time Frame: Measured from baseline and weekly for the duration of drug administration, estimated to be ≤1 year. ] [ Designated as safety issue: Yes ]
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.
Complete list of historical versions of study NCT01804530 on ClinicalTrials.gov Archive Site
  • Clinical Benefit Response Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Clinical Benefit Response Rate will be assessed by the primary measures of pain, analgesic consumption, and Karnofsky Performance Status and the secondary measure of weight.
  • Duration of response (DOR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Duration of response is defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: 6 month ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the number of days from start of therapy to the date of documented disease progression/relapse, whichever occurs first.
  • Overall response rate (ORR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall response rate (ORR) will be estimated as the number of patients with a best response of CR or PR divided by the total number of patients who are evaluable for efficacy.
  • Patient weight [ Time Frame: measured at each clinic visit for the duration of treatment, estimated to be ≤ 1 year. ] [ Designated as safety issue: No ]

    Change in patient weight from baseline.

    Positive: a weight gain of ≥7% from baseline, sustained for ≥4 weeks. Negative: any other result.

  • Pain intensity [ Time Frame: Measured daily from baseline for the duration of treatment, estimated to be ≤ 1 year. ] [ Designated as safety issue: No ]

    Changes in pain reported using the Memorial Pain Assessment Card.

    Positive: improvement of ≥50% from baseline sustained for 4 weeks, assuming minimum pain score of ≥20.

    Negative: any worsening from baseline, sustained for 4 weeks. Stable: any other result.

  • Analgesic consumption [ Time Frame: Measured weekly from baseline for the duration of treatment, estimated to be ≤ 1 year. ] [ Designated as safety issue: No ]

    Changes in analgesic requirements will be recorded daily by the paitent and measured weekly in morphine-equivalent milligrams.

    Positive: a decrease of ≥50% from baseline, sustained for ≥4 weeks, assuming a minimum analgesic consumption of ≥10.

    Negative: any worsening from baseline, sustained for 4 weeks. Stable: any other result.

  • Karnofsky Performance Status [ Time Frame: changes from baseline measured weekly for the duration of treatment, estimated to be ≤ 1 year. ] [ Designated as safety issue: No ]

    Changes in performance status from baseline, determined at each clinic visit.

    Positive: an improvement of ≥20 points from baseline, sustained for ≥4 weeks, for patients with performance status of 50, 60, or 70.

    Negative: any worsening of ≥20 points from baseline, sustained for ≥4 weeks. Stable: any other result.

  • Pharmacokinetics of PLX7486 [ Time Frame: first 21-days of drug administration ] [ Designated as safety issue: No ]
    The pharmacokinetics of PLX7486 will be analyzed by measurement of area under the plasma concentration-time curve [AUC0-t, AUC0-inf], peak concentration (Cmax), time to peak concentration (Tmax), half-life (t1/2), and terminal elimination rate constant (Kel).
Not Provided
  • Tumor response [ Time Frame: Patients that have received ≥2 administrations of gemcitabine + nab-paclitaxel and 21 days of PLX7486 ] [ Designated as safety issue: No ]
    Patients will be considered response evaluable if they have received ≥2 administrations of gemcitabine + nab-paclitaxel and 21 days of PLX7486 and have at least one post-baseline tumor assessment (except in cases of study discontinuation due to treatment-related toxicity or clinical progression).
  • Duration of remission (DOR) [ Time Frame: From documented initial response (PR or better) to disease progression/relapse, or death ] [ Designated as safety issue: No ]
    For each subject with a response to therapy, duration of remission will be calculated. The duration of remission is defined as the number of days from the date of the initial response (PR or better) to the date of the first documented disease progression/relapse or death, whichever occurs first.
  • Duration of complete remission (DOCR) [ Time Frame: From date of initial response to first documented disease relapse or death. ] [ Designated as safety issue: No ]
    For each subject with a complete remission, the duration of complete response will be calculated. Duration of complete remission is defined as the number of days from the date of initial CR response to the date of the first documented disease relapse or death, whichever occurs first.
  • Progression-Free Survival (PFS) [ Time Frame: number of days from start of therapy to the date of documented disease progression/relapse, or death ] [ Designated as safety issue: No ]
    For each subject with a response to therapy, progression-free survival will be calculated. Progression-Free Survival is defined as the number of days from start of therapy to the date of documented disease progression/relapse, or death, whichever occurs first.
  • Disease-Free Survival (DFS) [ Time Frame: From the date of the initial CR response to the date of documented disease relapse or death from any cause ] [ Designated as safety issue: No ]
    For subjects with a complete remission, the disease-free survival will be calculated from the date of the initial CR response to the date of documented disease relapse or death from any cause, whichever occurs first.
  • Overall response rate (ORR) [ Time Frame: Baseline to end of study, estimated to be ≤ 1 year. ] [ Designated as safety issue: No ]
    The overall response rate will be estimated as the number of patients with a best response of CR or PR divided by the total number of patients who are evaluable for efficacy. This analysis will be performed separately for Parts 1, 2a, and 2b.
 
Phase 1 Study of PLX7486 as Single Agent and With Gemcitabine Plus Nab-Paclitaxel in Patients With Advanced Solid Tumors
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
The goal of this clinical study is to learn how PLX7486 TsOH, Gemcitabine, and nab-Paclitaxel work together to affect the growth of cancer cells in advanced solid tumors.

Part 1 of this study is a sequential single-agent dose escalation of PLX7486-TsOH in patients with solid tumors.

Part 2a of this study is a sequential dose escalation of PLX7486-TsOH in combination with fixed doses of nab-Paclitaxel and Gemcitabine, This arm of the study is not recruiting patients.

Part 2b of this study is an extension cohort at the recommended phase 2 dose (RP2D) of PLX7486-TsOH in combination with fixed doses of nab-Paclitaxel and Gemcitabine in patients with untreated, advanced, non-resectable or metastatic pancreatic adenocarcinoma. This arm of the study is not recruiting patients.

Part 2c of this study is an extension cohort at the RP2D of PLX7486-TsOH in patients with advanced non-resectable tumors of any histology with activating Trk (NTRK) point or NTRK fusion mutations or with unresectable, locally advanced or refractory Tenosynovial giant cell tumor (TGCT), including metastatic disease.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Solid Tumors
  • Untreated Pancreatic Adenocarcinoma
  • Pancreatic Cancer Non-resectable
  • Metastatic Pancreatic Adenocarcinoma
  • Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations
  • Tenosynovial Giant Cell Tumor
  • Drug: PLX7486 TsOH
    PLX7486 TsOH capsules, 50mg
  • Drug: Gemcitabine
    Gemcitabine IV
    Other Name: Gemzar
  • Drug: nab-Paclitaxel
    nab-Paclitaxel IV
    Other Name: Abraxane
  • Experimental: PLX7486-TsOH, Dose escalation
    Part 1: Open-label, sequential PLX7486-TsOH single-agent dose escalation in approximately 50 patients with solid tumors.
    Intervention: Drug: PLX7486 TsOH
  • Experimental: PLX7486-TsOH with nab-Paclitaxel and Gemcitabine
    Part 2a: Open-label, sequential dose escalation of PLX7486-TsOH with fixed dose levels of nab-Paclitaxel + gemcitabine in approximately 30 patients with solid tumors. (Not recruiting)
    Interventions:
    • Drug: PLX7486 TsOH
    • Drug: Gemcitabine
    • Drug: nab-Paclitaxel
  • Experimental: RP2D of PLX7486-TsOH with nab-Paclitaxel and Gemcitabine
    Part 2b: Extension cohort at the RP2D of PLX7486-TsOH in combination with fixed dose levels of nab-paclitaxel + gemcitabine in approximately 50 patients with untreated, advanced, non-resectable or metastatic pancreatic adenocarcinoma. (Not recruiting)
    Interventions:
    • Drug: PLX7486 TsOH
    • Drug: Gemcitabine
    • Drug: nab-Paclitaxel
  • Experimental: PLX7486-TsOH, RP2D
    Part 2c: Extension cohort of single agent PLX7486-TsOH at the RP2D in patients with advanced non-resectable tumors of any histology with activating Trk (NTRK) point or NTRK fusion mutations or with unresectable, locally advanced or refractory Tenosynovial giant cell tumor (TGCT), including metastatic disease, in approximately 30 patients.
    Intervention: Drug: PLX7486 TsOH
Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
August 2021
February 2021   (final data collection date for primary outcome measure)

Inclusion Criteria

  • Male or female ≥18 years old
  • Patients with histologically confirmed solid tumors who:

    • Part 1: have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy
    • Part 2a: have received ≤2 prior chemotherapy regimens for the treatment of their primary malignancy and for whom nab-paclitaxel and gemcitabine would be considered a reasonable chemotherapy option
    • Part 2b: have previously untreated locally advanced, non-resectable or metastatic pancreatic adenocarcinoma that, in the opinion of the Principal Investigator, are not candidates for FOLFIRINOX treatment (i.e., bolus and infusional 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.
    • Part 2c:
    • Have advanced, non-resectable tumors of any histology with their growth driven by CSF-1R activity or activating Trk (NTRK) point or NTRK fusion mutations (e.g., mammary analogue secretory carcinoma, secretory breast cancer, papillary thyroid cancer, congenital fibrosarcoma, congenital mesoblastic nephroma, lung cancer, melanoma, and colon cancer) or underlying pathology or pathophysiology that suggests that NTRK signaling may be playing a significant role in disease (e.g., TrkC/NT3 overexpression in adenoid cystic carcinoma, TrkB/BDNF overexpression in non-small cell lung cancer) AND
    • have received prior treatment, if there is a known therapy that results in increased survival for that particular disease (e.g., patients with melanoma should have received treatment with ipilimumab or BRAF inhibitors, patients with colon cancer should have received at least 2 prior lines of therapy with a fluoropyrimidine in combination with oxaliplatin and irinotecan), OR
    • have unresectable, locally advanced or refractory TGCT (including metastatic disease)
  • Patients in Part 2b and 2c must have measurable disease by RECIST criteria v1.1
  • 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 (see Attachment 8) 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 (see Attachment 8) while on study drug and up to 3 months after the last dose of study drug.
  • All associated toxicity from previous or concurrent cancer therapy must be resolved (to ≤Grade 1 or Baseline) prior to study treatment administration
  • 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.
  • Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
  • Karnofsky performance status ≥70% (see Attachment 7)
  • Life expectancy ≥3 months
  • Adequate hematologic, hepatic, and renal function

Exclusion Criteria

  • 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
  • Chemotherapy within 28 days prior to C1D1
  • Biological therapy within 5 half-lives prior to C1D1
  • Radiation therapy within 28 days or 5 half-lives prior to C1D1, whichever is longer
  • Investigational drug use within 28 days or 5 half-lives, whichever is longer, prior to C1D1
  • Part 1 only: (a) Patients with active or a history of glucose intolerance or diabetes mellitus and (b) Hemoglobin A1c ≥7%
  • Part 2a and 2b only: Patients with a known hypersensitivity to nab-paclitaxel or gemcitabine
  • Part 2a, 2b, and 2c: Patients with uncontrolled diabetes or Hemoglobin A1c >8%. 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.
  • Part 2b only: Patients who have received radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic pancreatic adenocarcinoma. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
  • ≥Grade 2 sensory neuropathy at baseline
  • 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
  • Refractory nausea and vomiting, malabsorption, small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
  • Mean QTcF ≥450 msec (for males) or ≥470 msec (for females) at Screening
  • 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
Both
18 Years and older   (Adult, Senior)
No
Contact: Terry Cho tcho@plexxikon.com
United States
 
NCT01804530
PLX119-01
No
Not Provided
Not Provided
Plexxikon
Plexxikon
Not Provided
Not Provided
Plexxikon
June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP