Gastrointestinal NeoplasmsPhase 1UTAHNCT04145297
Ulixertinib (BVD-523) and Hydroxychloroquine in Patients W Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas
A Phase 1 study testing Ulixertinib and Hydroxychloroquine in people with Gastrointestinal Neoplasms, run by University of Utah at 1 site in United States.
Trial summary
Open-label dose escalation of Ulixertinib combined with fixed dose of hydroxychloroquine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms
- What is being tested?
- Ulixertinib and Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2020to 18 Aug 2022
- 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
- Male or female subject aged ≥ 18 years.
- Subject with histologically confirmed MAPK-mutated GI malignancies: KRAS, NRAS, HRAS, BRAFnon-V600, MEK, and ERK.
- Subject is willing to provide a baseline biopsy.
- Prior lines of therapy:
- For patients with cholangiocarcinoma: subject must have progressed during or after one line of therapy.
- For patients with pancreatic adenocarcinoma: the subject must have progressed during or after one line of therapy.
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- For patients with colorectal carcinoma: the subject must have progressed during or after two lines of therapy.
- For patients with stomach or esophageal carcinoma: the subject must have progressed during or after two lines of therapy.
- Subject must have measurable disease by RECIST 1.1 criteria by CT or MRI.
- ECOG Performance Status ≤ 1.
- Adequate organ function as defined as:
- Hematologic:
- Absolute neutrophil count (ANC) ≥ 1500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 10 g/dL
- Hepatic:
- Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
- Patients with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
- Renal:
- Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula:
- Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)
- Females: (((140-age)×weight[kg])/(serum creatinine [mg/dL]×72))×0.85
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Highly effective contraception for both male subjects and female subjects of child bearing potential throughout the study and for at least 4 months after last study treatment administration (see Section 7.6).
- Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Subject has received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy ≤ 14 days or within 5 half-lives prior to starting study treatment, whichever is shorter.
- Subject has received radiotherapy ≤ 14 days prior to the first dose of study treatment. Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe.
- Subjects who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not fully recovered from major surgery.
- Presence of peritoneal carcinomatosis (PC).
- Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration) or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms is allowed.
- Known brain metastases or cranial epidural disease.
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- --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
- Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
- Cardiovascular disorders:
- Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before first dose.
- QTc prolongation defined as a QTcF > 500 ms.
- History of seizures
- Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection under the judgment of the PI may impair absorption of study drugs).
- Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication.(patients may not receive drug through a feeding tube), social/ psychological issues, etc.
- Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
- --Note: Patients on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C.
- --Note: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.
- Known prior severe hypersensitivity to investigational product or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
- Subjects taking prohibited medications as described in Section 6.4. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Phase I Trial of Ulixertinib (BVD-523) and Hydroxychloroquine in Patients with Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas
Open-label dose escalation of Ulixertinib combined with fixed dose of hydroxychloroquine.
Read the detailed description
This is an open-label Phase I basket trial designed to determine the phase 2 recommended dose of ulixertinib in combination hydroxychloroquine. The recommended phase 2 dose (RP2D) will be determined by using a standard 3+3 dose-escalation design with a minimum of 3 evaluable subjects accrued to dose level one and two. Should dose level one be deemed intolerable, enrollment will proceed at dose level 0. The RP2D will be affirmed according to the rules of the 3+3 dose-escalation scheme
- Conditions
- Gastrointestinal Neoplasms
- Being tested
- Ulixertinib, Hydroxychloroquine
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UlixertinibDrug
Also called BVD-523
Ulixertinib will be provided as 150 mg capsules and will be self-administered twice daily by mouth at the assigned dose level.
Ulixertinib Dose Level 0 300 mg PO BID, Dose Level 1 (starting dose) 450 mg PO BID, Dose Level 2 600 mg PO BID,
Medication will be administered in 28-day cycles
Hydroxychloroquine will be provided as 200 mg tablets and will be self-administered by mouth twice daily. Fixed Dose 600mg POBID. Medication will be administered in 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Treatment: all patients | Experimental | Hydroxychloroquine will be provided as 200 mg tablets and will be self-administered by mouth twice daily.
Ulixertinib will be provided as 150 mg capsules and will be self-administered twice daily by mouth at the assigned dose level. Both medications will be administered in 28-day cycles Receives: Drug: Ulixertinib; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose of ulixertinib in combination with a fixed dose of hydroxychloroquine in subjects with advanced, RAS, non-V600 BRAF, ERK or MEK mutated gastrointestinal malignancies
The incidence of DLTs during the defined DLT period
Measured: the day of the first dose, cycle one day one, to cycle one day 28 (Cycle=28 days)
Secondary outcomes (2)
Safety and tolerability of ulixertinib and hydroxychloroquine in the study population: adverse events (AEs) and serious adverse events (SAEs)
The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment
Measured: Any patient who has taken at least one dose of both ulixertinib and hydroxychloroquine will be evaluable for toxicity. Assessment will be completed through safety follow-up visit at 60 days after the end of treatment visit.
Efficacy of ulixertinib and hydroxychloroquine in the study population: Objective response rate (PR and CR)
Objective response rate (PR and CR) will be described
Measured: Patients will be evaluable for response once they have completed the first cycle of treatment and completed the C2D1 CT Scan.Assessment will be completed through safety follow-up visit at 60 days after the end of treatment visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start17 Mar 2020
- Primary completion10 Jun 2022
- Study completion18 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- 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
- Model description
- Open-label dose escalation of Ulixertinib combined with fixed dose of hydroxychloroquine.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04145297
- Sponsor's protocol ID
- HCI127114
- Acronym
- UTAH
- Status last verified
- Nov 2024
- First submitted
- 28 Oct 2019
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Ulixertinib (BVD-523) and Hydroxychloroquine in Patients with Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas
- ClinicalTrials.gov ID
- NCT04145297
- Acronym / sponsor ID
- UTAH / HCI127114
- Conditions
- Gastrointestinal Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Study start
- 17 Mar 2020 (actual)
- Primary completion
- 10 Jun 2022 (actual)
- Study completion
- 18 Aug 2022 (actual)
- First posted
- 30 Oct 2019 (actual)
- 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.
Open-label dose escalation of Ulixertinib combined with fixed dose of hydroxychloroquine.
Detailed description
This is an open-label Phase I basket trial designed to determine the phase 2 recommended dose of ulixertinib in combination hydroxychloroquine. The recommended phase 2 dose (RP2D) will be determined by using a standard 3+3 dose-escalation design with a minimum of 3 evaluable subjects accrued to dose level one and two. Should dose level one be deemed intolerable, enrollment will proceed at dose level 0. The RP2D will be affirmed according to the rules of the 3+3 dose-escalation scheme
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label dose escalation of Ulixertinib combined with fixed dose of hydroxychloroquine.
| Arm | Type | Receives |
|---|---|---|
| Treatment: all patients | Experimental | Drug: Ulixertinib, Drug: HydroxychloroquineHydroxychloroquine will be provided as 200 mg tablets and will be self-administered by mouth twice daily. Ulixertinib will be provided as 150 mg capsules and will be self-administered twice daily by mouth at the assigned dose level. Both medications will be administered in 28-day cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Male or female subject aged ≥ 18 years.
- Subject with histologically confirmed MAPK-mutated GI malignancies: KRAS, NRAS, HRAS, BRAFnon-V600, MEK, and ERK.
- Subject is willing to provide a baseline biopsy.
- Prior lines of therapy:
- Subject must have measurable disease by RECIST 1.1 criteria by CT or MRI.
Key exclusion criteria (23 listed)
- Subject has received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy ≤ 14 days or within 5 half-lives prior to starting study treatment, whichever is shorter.
- Subject has received radiotherapy ≤ 14 days prior to the first dose of study treatment. Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe.
- Subjects who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not fully recovered from major surgery.
- Presence of peritoneal carcinomatosis (PC).
- Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, and low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration) or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms is allowed.
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 |
|---|---|---|
| UlixertinibAlso: BVD-523Ulixertinib will be provided as 150 mg capsules and will be self-administered twice daily by mouth at the assigned dose level. Ulixertinib Dose Level 0 300 mg PO BID, Dose Level 1 (starting dose) 450 mg PO BID, Dose Level 2 600 mg PO BID, Medication will be administered in 28-day cycles | Drug | Treatment: all patients |
| HydroxychloroquineHydroxychloroquine will be provided as 200 mg tablets and will be self-administered by mouth twice daily. Fixed Dose 600mg POBID. Medication will be administered in 28-day cycles | Drug | Treatment: all patients |
Primary outcome
Recommended phase 2 dose of ulixertinib in combination with a fixed dose of hydroxychloroquine in subjects with advanced, RAS, non-V600 BRAF, ERK or MEK mutated gastrointestinal malignancies
Time frame: the day of the first dose, cycle one day one, to cycle one day 28 (Cycle=28 days)
The incidence of DLTs during the defined DLT period
2 secondary outcomes
Safety and tolerability of ulixertinib and hydroxychloroquine in the study population: adverse events (AEs) and serious adverse events (SAEs)
Time frame: Any patient who has taken at least one dose of both ulixertinib and hydroxychloroquine will be evaluable for toxicity. Assessment will be completed through safety follow-up visit at 60 days after the end of treatment visit.
Efficacy of ulixertinib and hydroxychloroquine in the study population: Objective response rate (PR and CR)
Time frame: Patients will be evaluable for response once they have completed the first cycle of treatment and completed the C2D1 CT Scan.Assessment will be completed through safety follow-up visit at 60 days after the end of treatment visit.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ulixertinib and Hydroxychloroquine in people with Gastrointestinal Neoplasms, run by University of Utah at 1 site 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 29 inclusion and 23 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: finished, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Recommended phase 2 dose of ulixertinib in combination with a fixed dose of hydroxychloroquine in subjects with advanced, RAS, non-V600 BRAF, ERK or MEK mutated gastrointestinal malignancies (time frame: the day of the first dose, cycle one day one, to cycle one day 28 (Cycle=28 days)). 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 18 Nov 2024.