Phase I/IIa Study to Evaluate the Safety, PK, PD, and Preliminary Efficacy of PLX8394 in Patients With Advanced Cancers.

NCT02012231 | Terminated Phase 1

• 1 other identifier: PLX120-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Melanoma; Thyroid Cancer; Colorectal Cancer; Non-small Cell Lung Cancer; Cholangiocarcinoma; Histiocytosis; Hairy Cell Leukemia

Keywords

melanoma; anaplastic thyroid cancer; advanced papillary thyroid cancer; colorectal cancer; non-small cell lung cancer; cholangiocarcinoma; histiocytosis; hairy cell leukemia

Outcome Measures

Primary Outcomes (1)

• Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394

  Physical examinations, vital signs, 12-lead electrocardiograms, adverse events, hematology, serum chemistry, and urinalysis will be used to assess safety and tolerability.

  1 Year

Secondary Outcomes (1)

• Identification of Recommended Phase 2 dose (RP2D)

  1 year

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Cohort 1/Day -7 = 300 mg/day PLX8394; Cohort 1/Day 1 = 900 mg/day PLX8394

Drug: PLX8394

Interventions

PLX8394 DRUG

PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF.

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• \. 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
• \. EXTENSION COHORTS
• Cancers with a BRAF-activating mutation as assessed by a CLIA-certified method

You may not qualify if:

• 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

Sponsors & Collaborators

• Fore Biotherapeutics: lead

Study Sites (3)

Scottsdale Healthcare

Scottsdale, Arizona, 85258, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Evergreen Hematology & Oncology

Spokane, Washington, 99218, United States

Location

MeSH Terms

Conditions

Melanoma; Thyroid Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Histiocytosis; Leukemia, Hairy Cell; Thyroid Carcinoma, Anaplastic

Interventions

PLX8394

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Lymphatic Diseases; Hemic and Lymphatic Diseases; Leukemia; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sunil Sharma, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 16, 2013
• Study Start: February 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: June 1, 2015
• Last Updated: October 19, 2020

Record last verified: 2016-05

Locations

US (3)