MelanomaPhase 1NCT02012231
Phase I/IIa Study to Evaluate the Safety, PK, PD, and Preliminary Efficacy of PLX8394 in Patients With Advanced Cancers.
A Phase 1 study testing PLX8394 in people with Melanoma and Thyroid Cancer, run by Fore Biotherapeutics at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Thyroid Cancer, Colorectal Cancer
- What is being tested?
- PLX8394
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2014to Jun 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 19Show fewer
- 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
- 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
Who cannot join
- 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.
Show all 10Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
Scottsdale Healthcare
Scottsdale, Arizona, 85258
Evergreen Hematology & Oncology
Spokane, Washington, 99218
About this study
Official title: 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.
Read the detailed description
This is 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 130 patients are planned to be enrolled in the BRAF-mutated tumor Extension cohorts, with the goal of enrolling approximately 50 patients with BRAF/MEK/ERK inhibitor-naïve melanoma, approximately 10-15 patients with BRAF/MEK/ERK inhibitor-pretreated melanoma, approximately 50 patients with non-melanoma solid tumors, and approximately 10-15 patients with hairy cell leukemia. The trial was intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2.
- Conditions
- Melanoma, Thyroid Cancer, Colorectal Cancer, Non-small Cell Lung Cancer, Cholangiocarcinoma, Histiocytosis
- Being tested
- PLX8394
- Keywords
- melanoma, anaplastic thyroid cancer, advanced papillary thyroid cancer, colorectal cancer, non-small cell lung cancer, cholangiocarcinoma, histiocytosis, hairy cell leukemia
- Medical subject headings
- Melanoma, Thyroid Neoplasms, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Cholangiocarcinoma, Histiocytosis, Leukemia, Hairy Cell, Thyroid Carcinoma, Anaplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PLX8394Drug
PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | Cohort 1/Day -7 = 300 mg/day PLX8394; Cohort 1/Day 1 = 900 mg/day PLX8394 Receives: Drug: PLX8394 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 Year
Secondary outcomes (1)
Identification of Recommended Phase 2 dose (RP2D)
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startFeb 2014
- Primary completionSep 2014
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fore Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sunil Sharma, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012231
- Sponsor's protocol ID
- PLX120-01
- Status last verified
- May 2016
- First submitted
- 5 Dec 2013
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced, Unresectable Solid Tumors
- ClinicalTrials.gov ID
- NCT02012231
- Acronym / sponsor ID
- PLX120-01
- Conditions
- Melanoma, Thyroid Cancer, Colorectal Cancer, Non-small Cell Lung Cancer, Cholangiocarcinoma, Histiocytosis
- Keywords
- melanoma, anaplastic thyroid cancer, advanced papillary thyroid cancer, colorectal cancer, non-small cell lung cancer, cholangiocarcinoma, histiocytosis, hairy cell leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Fore BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Sep 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is 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 130 patients are planned to be enrolled in the BRAF-mutated tumor Extension cohorts, with the goal of enrolling approximately 50 patients with BRAF/MEK/ERK inhibitor-naïve melanoma, approximately 10-15 patients with BRAF/MEK/ERK inhibitor-pretreated melanoma, approximately 50 patients with non-melanoma solid tumors, and approximately 10-15 patients with hairy cell leukemia. The trial was intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: PLX8394Cohort 1/Day -7 = 300 mg/day PLX8394; Cohort 1/Day 1 = 900 mg/day PLX8394 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PLX8394PLX8394 is a next-generation, orally available, small-molecule, selective inhibitor of BRAF. | Drug | Dose Escalation |
Primary outcome
Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394
Time frame: 1 Year
Physical examinations, vital signs, 12-lead electrocardiograms, adverse events, hematology, serum chemistry, and urinalysis will be used to assess safety and tolerability.
1 secondary outcome
Identification of Recommended Phase 2 dose (RP2D)
Time frame: 1 year
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
Related trials for Melanoma
Enrolling by invitationObservational study
Community Based Strategies for Early Detection of Melanoma
Melanoma
Active, not recruitingPhase 3
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8
Active, not recruitingPhase 2
A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma
Acral Lentiginous Melanoma, Clinical Stage III Cutaneous Melanoma AJCC v8
RecruitingObservational study
Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Melanoma
Melanoma, Dysplastic Nevus Syndrome
RecruitingPhase 1
A Phase 1 Study to Evaluate OPB-201 in Recurrent Endometrial and Platinum-resistant Ovarian Cancer.
Endometrial Cancer Recurrent, Endometrial Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sunil Sharma, MD principal investigator
Huntsman Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PLX8394 in people with Melanoma and Thyroid Cancer, run by Fore Biotherapeutics at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1 dose escalation: Identification of Recommended Phase 2 Dose Safety of PLX8394 (time frame: 1 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.