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Histone Deacetylase Inhibitor

Neratinib + Valproate for Advanced Solid Cancers

Q: What maladies is Neratinib commonly utilized to treat?

Neratinib is commonly employed to treat <a href="https://www.withpower.com/clinical-trials/depression">depression</a>, however it may also prove efficacious for migraines, behcet syndrome, and complex partial seizures.

Q: What is the total enrollment capacity for this experiment?

Affirmative. According to clinicaltrials.gov, this research project is actively enrolling participants and has been advertised since May 1st of 2019. The most recent revision was made on September 22nd 2022 and the researchers are in search of 113 test subjects across one site location.

Q: Is the enrollment process for this research endeavor still ongoing?

Per the specifications on clinicaltrials.gov, this medical trial is actively seeking participants. The study was initially announced on May 1st 2019 and has been recently updated on September 22nd 2022.

Phase 1 & 2

Recruiting

Led By Andrew Poklepovic, MD

Research Sponsored by Virginia Commonwealth University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

All patients must meet all of the following inclusion criteria to be eligible to participate in the study: 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

Creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance ≥ 60 mL/min

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 13 months

Awards & highlights

Study Summary

This trial is testing the recommended dose of a combination of neratinib and sodium valproate for patients with advanced solid tumors. The expansion cohort will explore the effects of the combination on tumors with RAS mutations, EGFR alterations, and ocular melanoma.

Who is the study for?

This trial is for adults with advanced solid tumors, including specific types such as RAS-mutated colon or pancreatic cancer, ocular melanoma, and glioblastoma with RAS mutation or EGFR alteration. Participants must have progressed after standard treatments or have no effective options available. They should be in good physical condition (ECOG 0-1), not pregnant, willing to use contraception, able to swallow pills without malabsorption issues, and free from serious infections or heart conditions.Check my eligibility

What is being tested?

The study aims to find the safest dose of neratinib combined with sodium valproate that can be given to patients with advanced solid tumors. It will also assess how well this combination works against certain tumor types like those with RAS mutations and EGFR-altered glioblastomas.See study design

What are the potential side effects?

Potential side effects include diarrhea which could lead to dehydration if uncontrolled; blood pressure changes; possible interactions leading to cardiac issues; risk of seizures for those on certain antiepileptic medications; and liver function alterations due to hepatitis B/C.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My kidney function, measured by creatinine levels, is within the normal range.

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It's been at least 12 weeks since I finished radiation therapy for my brain tumor.

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I am a woman under 60, have not had a hysterectomy, and tested negative for pregnancy recently.

Select...

My cancer is advanced, has a RAS mutation or specific changes, and has not responded to standard treatments.

Select...

I am fully active or can carry out light work.

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My cancer is advanced, has a RAS mutation, and has not responded to standard treatments.

Select...

My bone marrow is working well.

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My advanced cancer has worsened despite treatment, or there's no effective treatment for it.

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My solid tumor can be measured or evaluated by standard criteria.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 13 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~13 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 13 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Determination of Recommended Phase 2 Dose (RP2D)

Secondary outcome measures

Sodium valproate

Glioblastoma Antitumor Effects

Progression Free Survival (PFS)

+1 more

Side effects data

From 2022 Phase 2 trial • 11 Patients • NCT03094052

100%

Diarrhea

100%

Constipation

82%

Nausea

45%

Fatigue

45%

Abdominal distension

36%

Headache

36%

Dizziness

27%

Hot flashes

27%

Pruritus

27%

Dyspnea

27%

Weight loss

27%

Vomiting

27%

Anorexia

18%

Dysgeusia

18%

Alanine aminotransferase increased

18%

Aspartate aminotransferase increased

18%

Fever

18%

Gastrointestinal disorders - Other, specify

18%

Abdominal pain

18%

Bloating

18%

Sinus bradycardia

18%

Skin and subcutaneous tissue disorders - Other, specify

Anxiety

Cholecystitis

Mucositis oral

Paresthesia

Rash maculo-papular

Upper respiratory infection

Fracture

Back pain

Joint range of motion decreased

Vaginal dryness

Lymphedema

Anal hemorrhage

Muscle weakness upper limb

Musculoskeletal and connective tissue disorder - Other, specify

Vaginal hemorrhage

Chills

Vaginal discharge

Gastroesophageal reflux disease

Creatinine increased

Bruising

Vaginal infection

Arthralgia

Pain

Urinary tract pain

Wheezing

Ejection fraction decreased

Peripheral sensory neuropathy

Insomnia

Flatulence

Flu like symptoms

Rash acneiform

Oral dysesthesia

Stomach pain

General disorders and administration site conditions - Other, specify

Infections and infestations - Other, specify

Fall

Neck pain

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Neratinib)

Trial Design

6Treatment groups

Experimental Treatment

Group I: Pancreatic CancerExperimental Treatment2 Interventions

RAS-mutated pancreatic cancer at RP2D

Group II: Other CancerExperimental Treatment2 Interventions

"Other Cancer" (RAS-mutated) at RP2D

Group III: Ocular Melanoma (OM)Experimental Treatment2 Interventions

Phase II dose expansion at RP2D

Group IV: Neratinib + Divalproex Sodium - Dose Escalation CohortExperimental Treatment2 Interventions

Neratinib by mouth (PO) once daily + Divalproex Sodium (Valproate) by mouth (PO) twice daily on days 1-28 of each course.

Group V: Glioblastoma (GBM)Experimental Treatment2 Interventions

Glioblastoma with a RAS-mutation or EGFR alteration at RP2D

Group VI: ColonExperimental Treatment2 Interventions

Colon Cancer (RAS-mutated) - Phase II dose expansion at recommended phase II dose (RP2D)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Neratinib

2014

Completed Phase 2

~1970

Divalproex Sodium

2006

Completed Phase 4

~560

0 / 10Eligibility criteria met

Find a Location

Who is running the clinical trial?

Puma Biotechnology, Inc.Industry Sponsor

57 Previous Clinical Trials

9,829 Total Patients Enrolled

Virginia Commonwealth UniversityLead Sponsor

698 Previous Clinical Trials

22,884,882 Total Patients Enrolled

Andrew Poklepovic, MDPrincipal InvestigatorMassey Cancer Center

4 Previous Clinical Trials

132 Total Patients Enrolled

Media Library

Divalproex Sodium (Histone Deacetylase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03919292 — Phase 1 & 2

Solid Tumors Research Study Groups: Neratinib + Divalproex Sodium - Dose Escalation Cohort, Colon, Ocular Melanoma (OM), Pancreatic Cancer, Glioblastoma (GBM), Other Cancer

Solid Tumors Clinical Trial 2023: Divalproex Sodium Highlights & Side Effects. Trial Name: NCT03919292 — Phase 1 & 2

Divalproex Sodium (Histone Deacetylase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03919292 — Phase 1 & 2

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What maladies is Neratinib commonly utilized to treat?

"Neratinib is commonly employed to treat depression, however it may also prove efficacious for migraines, behcet syndrome, and complex partial seizures."

Answered by AI

What is the total enrollment capacity for this experiment?

"Affirmative. According to clinicaltrials.gov, this research project is actively enrolling participants and has been advertised since May 1st of 2019. The most recent revision was made on September 22nd 2022 and the researchers are in search of 113 test subjects across one site location."

Answered by AI

Is the enrollment process for this research endeavor still ongoing?

"Per the specifications on clinicaltrials.gov, this medical trial is actively seeking participants. The study was initially announced on May 1st 2019 and has been recently updated on September 22nd 2022."

Answered by AI

Recent research and studies

Pigment Cell & Melanoma ResearchJournal

Neratinib Kills B‐RAF V600E Melanoma via Ros‐dependent Autophagosome Formation and Death Receptor Signaling

Dent, Paul, Laurence Booth, Andrew Poklepovic, and John M. Kirkwood. 2021. “Neratinib Kills B‐RAF V600E Melanoma via Ros‐dependent Autophagosome Formation and Death Receptor Signaling”. Pigment Cell & Melanoma Research. Wiley. doi:10.1111/pcmr.13014.

clinicaltrials.govStudy

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

2019. "Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03919292.