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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca

Phase 1/2 Study of Neratinib and Divalproex Sodium (Valproate) in Advanced Solid Tumors, With an Expansion Cohort in Ras-Mutated Cancers

Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca (NCT03919292) is a Phase 1 / Phase 2 interventional studying Solid Tumor, Adult, sponsored by Virginia Commonwealth University. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

To determine the recommended phase 2 dose (RP2D) of the combination of neratinib and sodium valproate when given to patients with advanced solid tumors. Then to explore the antitumor effects of the neratinib and sodium valproate combination in advanced solid tumors with attention to RAS-mutated tumors, EGFR-altered GBM, and ocular melanoma, as part of the phase 2 expansion cohort.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Solid Tumor, Adult, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 83 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Solid Tumor, Adult subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Phase 1 - Dose Escalation Phase: Advanced solid tumor that has progressed during or after treatment with approved therapies or for which there is no standard effective therapy available - Phase 2 - Dose Expansion Phase: One of the following advanced solid tumors that is RAS-mutated and has progressed during or after treatment with at least one approved therapy or for which there is no standard effective therapy available: : - Colon Cancer with a RAS mutation - Pancreatic Cancer with a RAS mutation - Other Solid Tumor with RAS Mutation - Ocular melanoma, which includes melanoma that develops in the sclera, retina, uvea (iris, choroid layer, and ciliary layer), or conjunctiva or other cancers with a GNAQ or GNA11 mutation - Measurable disease by RECIST v1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate bone marrow function - Absolute neutrophil count (ANC) ≥ 1500/mm3 - platelet count at least 100,000/mm3 - Hemoglobin \> 9 g/dL (untransfused) - Adequate renal function - Creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual kidney function (creatinine clearance) at least 60 mL/min - Adequate hepatic function - Total bilirubin ≤ 1.5 x ULN for the laboratory Exception: If a patient has documented Gilbert's syndrome and a total bilirubin is \> 1.5 x ULN for the laboratory, the total bilirubin requirement may be waived provided the direct bilirubin is within normal limits (WNL) for the laboratory. - Aspartate aminotransferase (AST) ≤ 3.0 x ULN for the laboratory - Alanine aminotransferase (ALT) ≤ 3.0 x ULN for the laboratory - Note: For the expansion cohorts, in patients with documented liver metastasis, the AST and ALT requirements will be ≤ 5 x ULN for the laboratory ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * Phase 1 - Dose Escalation Phase: Advanced solid tumor that has progressed during or after treatment with approved therapies or for which there is no standard effective therapy available * Phase 2 - Dose Expansion Phase: One of the following advanced solid tumors that is RAS-mutated and has progressed during or after treatment with at least one approved therapy or for which there is no standard effective therapy available: : * Colon Cancer with a RAS mutation * Pancreatic Cancer with a RAS mutation * Other Solid Tumor with RAS Mutation * Ocular melanoma, which includes melanoma that develops in the sclera, retina, uvea (iris, choroid layer, and ciliary layer), or conjunctiva or other cancers with a GNAQ or GNA11 mutation * Measurable disease by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate bone marrow function * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelets ≥ 100,000/mm3 * Hemoglobin \> 9 g/dL (untransfused) * Adequate renal function * Creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance ≥ 60 mL/min * Adequate hepatic function * Total bilirubin ≤ 1.5 x ULN for the laboratory Exception: If a patient has documented Gilbert's syndrome and a total bilirubin is \> 1.5 x ULN for the laboratory, the total bilirubin requirement may be waived provided the direct bilirubin is within normal limits (WNL) for the laboratory. * Aspartate aminotransferase (AST) ≤ 3.0 x ULN for the laboratory * Alanine aminotransferase (ALT) ≤ 3.0 x ULN for the laboratory * Note: For the expansion cohorts, in patients with documented liver metastasis, the AST and ALT requirements will be ≤ 5 x ULN for the laboratory * Non-hematologic toxicities from previous cancer therapies resolved to ≤ grade 1 except chronic residual toxicities that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profiles of neratinib and sodium valproate (eg, alopecia, changes in pigmentation, stable endocrinopathies, neuropathy, skin toxicities) * International normalized ratio (INR) is ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN for the laboratory * A woman of childbearing potential (WCBP), defined as a woman who is \< 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 7 days prior to initiating study treatment * WCBP and a male patient with a partner who is a WCBP must agree to use a medically accepted method for preventing pregnancy for the duration of study treatment and for 2 months following completion of study treatment * Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Current or prior known meningeal metastases Known brain metastases that are symptomatic or untreated Note: Patients with known brain metastases who are asymptomatic and have had post-treatment imaging that indicates stable brain disease are eligible. Note that brain imaging in patients with known brain metastases is required within 8 weeks prior to initiation of study therapy. * Any investigational agent within 4 weeks prior to initiating study treatment * Previous therapy with neratinib * Active uncontrolled diarrhea leading to dehydration or electrolyte disturbances not easily controlled with oral repletion * Inability to swallow medication * Known or suspected malabsorption condition or obstruction. Note: Use of pancreatic enzyme supplements is allowed to control malabsorption * Inability to shift medications as follows: Antacids (eg, calcium carbonate): dose at least 3 hours after dosing with neratinib. H2 receptor antagonists: dose must be taken at least 2 hours after or 10 hours before dosing with neratinib * Resting systolic blood pressure (BP) \< 100 mmHg * Active or clinically significant cardiac disease including any of the following: * Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment * Myocardial infarction diagnosed within 6 months prior to initiating study treatment * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers * New York Heart Association (NYHA) class III or IV congestive heart failure * Seizure disorder requiring an enzyme inducing antiepileptic medication (EIAED) * Serious (ie, ≥ grade 3) uncontrolled infection * Chronic or active hepatitis B or C infection with elevated transaminase levels * Pleural effusion or ascites that causes respiratory compromise (ie, ≥ grade 2 dyspnea) * Known mitochondrial disorder caused by mutations in mitochondrial DNA polymerase gamma (γ) * Known urea cycle disorders * Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment: * Cosyntropin * Proton pump inhibitors (PPIs) * High-risk P-glycoprotein (P-gp) substrates (eg, digoxin, dabigatran, fexofenadine). Other anticoagulants are not considered high-risk P-gp substrates * Strong or moderate CYP3A4 inhibitors and/or Strong or moderate CYP3A4 inducers. Examples of clinical inhibitors and clinical inducers for P450-mediated metabolism and classification of strong, moderate, and weak interactions are available through the FDA website, Tables 3-2 and 3-3: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm Note: If such medications have been used, patients must have discontinued these agents ≥ 2 weeks prior to initiating study treatment * Pregnancy or breastfeeding * Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Treatments Being Tested

DRUG

Neratinib

Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion). Doses of Neratinib are escalated in small groups of patients during the dose expansion portion of the study.

DRUG

Divalproex Sodium

Combination of Neratinib and Divalproex Sodium (Valproate) will be given to patients with advanced solid tumors (dose escalation) and Ras-mutated cancers (dose expansion).

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03919292), the sponsor (Virginia Commonwealth University), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03919292 clinical trial studying?

To determine the recommended phase 2 dose (RP2D) of the combination of neratinib and sodium valproate when given to patients with advanced solid tumors. Then to explore the antitumor effects of the neratinib and sodium valproate combination in advanced solid tumors with attention to RAS-mutated tumors, EGFR-altered GBM, and ocular melanoma, as part of the phase 2 expansion cohort. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03919292?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03919292?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03919292. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03919292. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.