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mTOR Inhibitor

Neratinib + Targeted Therapy for Advanced Cancer

Phase 1

Waitlist Available

Led By Sarina A Piha-Paul

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Subjects must have somatic mutation in KRAS (Patients will be enrolled only on neratinib and trametinib combination ARM)

Any prior neuropathy should be back to baseline or grade 1

Must not have

Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization

Uncontrolled concurrent disease or illness including but not limited to symptomatic congestive heart failure, unstable or untreated cardiac conditions, diabetes mellitus, psychiatric illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Approved for 10 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing neratinib in combination with everolimus, palbociclib, or trametinib to see if it is effective in treating solid tumors that have progressed despite prior treatment and have spread to other parts of the body.

Who is the study for?

Adults with advanced or metastatic solid tumors that are unresponsive to standard treatments and have specific genetic mutations (EGFR, HER2, HER3/4, KRAS) may join. They should be in good physical condition (ECOG 0-1), have adequate organ function, not be pregnant or breastfeeding, agree to use contraception, and not have certain health conditions like active infections or recent major surgery.

What is being tested?

The trial is testing the effectiveness of neratinib combined with everolimus, palbociclib, or trametinib on patients whose tumors carry certain mutations. It aims to find the safest doses and observe how well these drug combinations can control tumor growth compared to neratinib alone.

What are the potential side effects?

Potential side effects include diarrhea from neratinib; mouth sores and weakened immune system from everolimus; low white blood cell counts leading to increased infection risk from palbociclib; and skin rash as well as vision changes from trametinib. Each drug combination has its own set of possible side effects.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a KRAS mutation.

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My previous nerve pain or damage has improved to mild or gone.

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My skin rash is mild before starting trametinib.

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My cancer does not respond to standard treatments anymore.

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I am fully active or can carry out light work.

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My cancer has mutations in the EGFR or HER family genes.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not currently hospitalized for an infection or serious illness.

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I do not have any uncontrolled illnesses like heart failure or untreated diabetes.

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I need immunosuppressive drugs for my autoimmune disorder.

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I have an active brain tumor or cancer spread to my brain or its coverings.

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I have been diagnosed with Hepatitis B, C, or HIV.

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I have a stomach or intestine problem that affects how my body absorbs medicine.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) of neratinib when given in combination with everolimus, palbociclib, or trametinib

Secondary study objectives

Determination of pharmacodynamics markers in tissue, blood, and plasma

Incidence of adverse events of neratinib when given in combination with everolimus, palbociclib, or trametinib

Objective response

Side effects data

From 2022 Phase 2 trial • 11 Patients • NCT03094052

100%

Diarrhea

100%

Constipation

82%

Nausea

45%

Abdominal distension

45%

Fatigue

36%

Dizziness

36%

Headache

27%

Dyspnea

27%

Hot flashes

27%

Anorexia

27%

Vomiting

27%

Pruritus

27%

Weight loss

18%

Skin and subcutaneous tissue disorders - Other, specify

18%

Dysgeusia

18%

Bloating

18%

Fever

18%

Abdominal pain

18%

Gastrointestinal disorders - Other, specify

18%

Aspartate aminotransferase increased

18%

Alanine aminotransferase increased

18%

Sinus bradycardia

Back pain

Neck pain

Rash acneiform

Rash maculo-papular

Lymphedema

Muscle weakness upper limb

Vaginal dryness

Anal hemorrhage

Paresthesia

Gastroesophageal reflux disease

Pain

Infections and infestations - Other, specify

Urinary tract pain

Flu like symptoms

Fracture

Flatulence

Mucositis oral

Chills

General disorders and administration site conditions - Other, specify

Ejection fraction decreased

Oral dysesthesia

Peripheral sensory neuropathy

Creatinine increased

Upper respiratory infection

Vaginal infection

Stomach pain

Bruising

Fall

Joint range of motion decreased

Musculoskeletal and connective tissue disorder - Other, specify

Arthralgia

Vaginal discharge

Vaginal hemorrhage

Wheezing

Anxiety

Insomnia

Cholecystitis

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Neratinib)

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm III (neratinib, trametinib)Experimental Treatment2 Interventions

Participants receive neratinib PO daily and trametinib PO daily as directed. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (neratinib, palbociclib)Experimental Treatment2 Interventions

Participants receive Neratinib PO daily for 28 days and Palbociclib PO daily for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: Arm I (neratinib, everolimus)Experimental Treatment2 Interventions

Participants receive neratinib PO daily and everolimus PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Everolimus

FDA approved

Neratinib

FDA approved

Palbociclib

FDA approved

Trametinib

FDA approved