- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02012231
Phase I/IIa Study to Evaluate the Safety, PK, PD, and Preliminary Efficacy of PLX8394 in Patients With Advanced Cancers.
A Phase I/IIa Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced, Unresectable Solid Tumors
The study objective is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered PLX8394 in patients with advanced solid tumors. An additional objective is to identify a Recommended Phase 2 (RP2D) for further evaluation in the Extension Cohorts (Phase IIa portion).
The study objective of the Extension Cohorts (PART 2 portion) is to assess the objective tumor response and the PK, PD, and safety of PLX8394 when the RP2D is used in patients with advanced BRAF-mutated cancers.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85258
- Scottsdale Healthcare
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Utah
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Salt Lake City, Utah, United States, 84112
- Huntsman Cancer Institute
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Washington
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Spokane, Washington, United States, 99218
- Evergreen Hematology & Oncology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years
- Measurable 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.
- Completion of previous chemotherapy, immunotherapy, or radiation therapy at least 2 weeks before study drug initiation, with resolution of all associated toxicity (to ≤ Grade 1 or Baseline)
- Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements
Eligibility for medical insurance coverage
1. DOSE-ESCALATION COHORTS
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
2. EXTENSION COHORTS
Cancers with a BRAF-activating mutation as assessed by a CLIA-certified method
a. Melanoma
- unresectable Stage IIIC or Stage IV disease (sub-cohort 1a: BRAF/MEK/ERK inhibitor naïve, sub-cohort 1b: BRAF/MEK/ERK inhibitor pre-treated) b. 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, cholangiocarcinoma, etc) 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 c. 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
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. Examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, and isolated elevation of prostate-specific antigen. Patients with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose Escalation
Cohort 1/Day -7 = 300 mg/day PLX8394; Cohort 1/Day 1 = 900 mg/day PLX8394
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PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394
Time Frame: 1 Year
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Physical examinations, vital signs, 12-lead electrocardiograms, adverse events, hematology, serum chemistry, and urinalysis will be used to assess safety and tolerability.
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1 Year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identification of Recommended Phase 2 dose (RP2D)
Time Frame: 1 year
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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.
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1 year
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lung Diseases
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Endocrine Gland Neoplasms
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Thyroid Diseases
- Head and Neck Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Lung Neoplasms
- Leukemia
- Neuroendocrine Tumors
- Nevi and Melanomas
- Carcinoma, Non-Small-Cell Lung
- Colorectal Neoplasms
- Melanoma
- Cholangiocarcinoma
- Thyroid Neoplasms
- Histiocytosis
- Leukemia, Hairy Cell
Other Study ID Numbers
- PLX120-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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