Trial record 10 of 62 for:    Open Studies | "Leukemia, Hairy Cell"

Phase 1 Study of Patients With Advanced, Unresectable Solid Tumors and Hairy Cell Leukemia Refractory

This study is not yet open for participant recruitment.
Verified December 2013 by Plexxikon
Information provided by (Responsible Party):
Plexxikon Identifier:
First received: December 5, 2013
Last updated: December 10, 2013
Last verified: December 2013

The study objective is to evaluate the safety and pharmacokinetics (PK) of orally administered PLX8394 in patients with solid tumors. An additional objective is to identify a Recommended Phase 2 (RP2D) for further evaluation in the Extension Cohorts.

Condition Intervention Phase
Solid Tumors
Hairy Cell Leukemia
Drug: PLX8394
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced, Unresectable Solid Tumors and Hairy Cell Leukemia Refractory to Standard Therapy

Resource links provided by NLM:

Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394 [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Physical examinations, vital signs, 12-lead electrocardiograms, adverse events, hematology, serum chemistry, and urinalysis will be used to assess safety and tolerability.

Secondary Outcome Measures:
  • Identification of Recommended Phase 2 dose (RP2D) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    For solid tumor, study drug administration is dosed continuously until clinically significant disease progression, discontinuation of study for any reason or one of the stopping criteria is met.

    For hairy cell leukemia, study drug administration is planned for a minimum of 2 cycles (6 weeks) up to a maximum of 8 cycles (6 months).

    • If a CR without MRD is achieved at the completion of the initial 2 or 4 cycles, patients will discontinue study drug (End of Study).
    • If a CR with MRD, or PR is achieved at the completion of the initial 4 cycles, patients will continue study drug for up to 4 additional cycles (End of Study).
    • If there is no response after the initial 4 cycles of study drug, patient will be removed from the study.

Estimated Enrollment: 42
Study Start Date: February 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation
300 mg/day PLX8394 cohort 900 mg/day PLX8394
Drug: PLX8394
PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF.
Other Name: PLX8394

Detailed Description:

This will be an open-label, multi-center Phase I/IIa two-part study with a sequential dose escalation part, followed by three parallel Extension cohorts (BRAF-mutated melanoma, BRAF-mutated non-melanoma solid tumors, and BRAF-mutated classical hairy cell leukemia). Up to approximately 42 patients may be enrolled in the dose escalation phase of the study, depending on the number of cohorts required, number of patients per cohort needed, and the need for replacement patients. Approximately 50 patients are planned to be enrolled in the BRAF-mutated tumor Extension cohorts, with the goal of enrolling approximately 10-15 patients with BRAF-mutated hairy cell leukemia, approximately10-15 patients with BRAF mutated anaplastic thyroid carcinoma, approximately 10-15 patients with BRAF mutated papillary carcinoma, and the remainder with other BRAF-mutated solid tumors.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Main Inclusion Criteria:


  • advanced solid tumors that are refractory to standard therapy, have no standard therapy, or are considered by the investigator to be inappropriate for standard therapy EXTENSION COHORTS
  • cancers with a BRAF-activating mutation as assessed by a CLIA-certified method


  • resectable Stage IIIc or Stage IV disease (sub-cohort 1a: BRAF/MEK/ERK inhibitor naïve, sub-cohort 1b: BRAF/MEK/ERK inhibitor pre-treated)

    *Non-melanoma Solid Tumors

  • advanced anaplastic thyroid cancer, advanced papillary thyroid cancer, and advanced solid tumors (e.g., colorectal cancer, non-small cell lung cancer) that are refractory to standard therapy, relapsed after standard therapy, have no standard therapy, or are considered by the investigator to be inappropriate for standard therapy

    *Hairy Cell Leukemia

  • histologically confirmed classical hairy cell leukemia that failed to achieve CR or PR to initial purine analog-based therapy, relapsed ≤ 2 years after purine analog-based therapy, or a history of intolerance to purine analogs


  • Age ≥ 18 years
  • Measureable disease by RECIST 1.1 criteria (solid tumors)
  • ECOG performance status of 0-2
  • Life expectancy ≥ 3 months
  • Adequate hematologic, hepatic, and renal function:

    • Solid Tumors — Absolute neutrophil count ≥ 1.5 × 109/L, Hgb > 9 g/dL, platelet count ≥ 100 × 109/L, AST/ALT ≤ 2.5 × ULN, bilirubin ≤ 2, creatinine ≤ 1.5 × ULN or calculated CrCl >50 mL/min (Cockcroft-Gault formula).
    • Hairy Cell Leukemia — Absolute neutrophil count ≤ 1.0 × 109/L, Hgb ≤ 10.0 g/dL or platelet count ≤ 100 × 109/L; AST/ALT ≤ 2.5 × ULN, bilirubin ≤ 2, creatinine ≤ 1.5 × ULN or calculated CrCl >50 mL/min (Cockcroft-Gault formula)
  • Women of child-bearing potential must have a negative serum pregnancy test within 14 days of initiating study drug and must agree to use an acceptable method of birth control from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Urine pregnancy testing during the study and in follow-up per country specific requirements. Fertile men must also agree to use an acceptable method of birth control while on study drug and up to 6 months after the last dose of study drug

Main Exclusion Criteria:

  • Extension Cohorts (except 1b) — Previous treatment with a selective BRAF/MEK/EKR inhibitor
  • Symptomatic brain metastases. Patients with untreated brain metastasis ≤ 1 cm can be considered eligible if deemed asymptomatic by the investigator upon consultation with the medical monitor and do not require immediate radiation or steroids. Patients with brain metastasis that is treated and stable for 1 month may be considered eligible if they are asymptomatic and on stable dose of steroids or if they do not require steroids following successful local therapy
  • Investigational drug use within 28 days (or < 5 half-lives, whichever is shorter) of the first dose of PLX8394
  • Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study
  • Uncontrolled intercurrent illness
  • Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
  • Baseline mean QTcF ≥ 450 ms (males) or ≥ 470 ms (females)
  • Women who are breast-feeding or pregnant
  • Known chronic HIV, HCV, or HBV infection
  Contacts and Locations
Please refer to this study by its identifier: NCT02012231

Contact: Bao Lam, MD 510-647-4008

United States, Utah
Huntsman Cancer Institute Not yet recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Principal Investigator: Sunil Sharma, MD Huntsman Cancer Institute
  More Information

No publications provided

Responsible Party: Plexxikon Identifier: NCT02012231     History of Changes
Other Study ID Numbers: PLX120-01
Study First Received: December 5, 2013
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Hairy Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases processed this record on April 17, 2014