← Back to Search

Aurora Kinase Inhibitor

Alisertib + Osimertinib for Lung Cancer

Phase 1

Recruiting

Led By Collin Blakely, MD, PhD

Research Sponsored by Collin Blakely

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Currently receiving and tolerating osimertinib 80 mg PO daily with no current grade 2 or greater AE attributable to osimertinib.

Must not have

Patients currently receiving treatment with contraindicated medications or potent CYP3A4 inducers/inhibitors.

Known Gastrointestinal (GI) disease or GI procedures that could interfere with the oral absorption or tolerance of alisertib.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the side effects and best dose of alisertib when given with osimertinib for patients with EGFR-mutated stage IV lung cancer.

Who is the study for?

Adults with stage IV lung cancer characterized by specific EGFR mutations, who are currently taking and tolerating osimertinib. They must have good performance status, measurable disease, acceptable lab values, agree to provide samples for research, use contraception if applicable, and not be pregnant or breastfeeding. Excluded are those with certain brain metastases, extensive prior radiation therapy, severe medical conditions or those on conflicting medications.

What is being tested?

This trial is testing the combination of two drugs: Alisertib (which blocks a protein that may help lung cancer grow) and Osimertinib (which targets mutant proteins to reduce tumor growth). The study aims to determine the safest dose of Alisertib when used with Osimertinib and observe their effects on advanced-stage lung cancer.

What are the potential side effects?

Potential side effects include issues related to blocking Aurora Kinase A by Alisertib which could affect cell division leading to blood disorders or fatigue; while Osimertinib might cause skin reactions or diarrhea due to its action on EGFR. Both drugs' interactions can also result in unforeseen side effects.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am fully active or can carry out light work.

Select...

I am taking osimertinib 80 mg daily without severe side effects.

Select...

I am following the required contraceptive measures.

Select...

I am following the required birth control guidelines.

Select...

My lung cancer is confirmed to be stage IV non-small cell type.

Select...

My cancer has a specific EGFR mutation, confirmed by a certified lab test.

Exclusion Criteria

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

Select...

I am not on medication that interferes with the study drugs.

Select...

I do not have any stomach or intestine problems that could affect how a medicine is absorbed.

Select...

I have uncontrolled sleep apnea or conditions causing excessive daytime sleepiness.

Select...

My cancer has spread to the lining of my brain and spinal cord.

Select...

I am not pregnant or breastfeeding.

Select...

I cannot take pills or follow the treatment plan for alisertib.

Select...

I have received radiation therapy to a large portion of my bone marrow.

Select...

I have brain metastases and am not stable neurologically.

Select...

I have not been diagnosed or treated for another cancer within the last 3 years.

Select...

I have a history of serious heart conditions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Determination of Maximum Tolerated Dose (MTD) (Cohort A)

Proportion of patients experiencing dose limiting toxicity (DLT) (Cohort A)

Proportion of patients experiencing serious adverse event (SAE)

Secondary study objectives

Amount of time (maximum) drug concentration in serum (Tmax)

Area Under Curve (AUC)

Central Nervous System (CNS) disease control rate

+8 more

Side effects data

From 2017 Phase 2 trial • 178 Patients • NCT02038647

55%

Diarrhoea

47%

Neutropenia

44%

Anaemia

44%

Fatigue

34%

Nausea

33%

Decreased appetite

32%

Vomiting

31%

Stomatitis

24%

Dyspnoea

20%

Cough

17%

Dizziness

16%

Asthenia

16%

Neutrophil count decreased

16%

Alopecia

15%

Weight decreased

14%

White blood cell count decreased

14%

Abdominal pain

14%

Leukopenia

11%

Hypokalaemia

10%

Febrile neutropenia

10%

Headache

10%

Arthralgia

Dyspepsia

Constipation

Pyrexia

Neuropathy peripheral

Dehydration

Abdominal pain upper

Thrombocytopenia

Hypocalcaemia

Insomnia

Oedema peripheral

Muscular weakness

Fall

Hypertension

Hyperglycaemia

Gastrooesophageal reflux disease

Dysphagia

Hypomagnesaemia

Dysphonia

Somnolence

Back pain

Non-cardiac chest pain

Productive cough

Paraesthesia

Hypoaesthesia

Musculoskeletal pain

General physical health deterioration

Pneumonia

Respiratory failure

Epistaxis

Pain in extremity

Upper respiratory tract infection

Neutropenic sepsis

Lung neoplasm malignant

Pulmonary embolism

Dysgeusia

Confusional state

Glioblastoma

Pancytopenia

Bacteraemia

Oral herpes

Sepsis

Septic shock

Influenza

Respiratory tract infection

Fungal infection

Tumour pain

Metastases to meninges

Acute respiratory failure

Acute coronary syndrome

Systemic inflammatory response syndrome

Seizure

Pulmonary oedema

Cardiac failure

Diabetic metabolic decompensation

Ataxia

Mental status changes

Aortic thrombosis

Paraplegia

Bile duct stenosis

Embolism

100%

80%

60%

40%

20%

Study treatment Arm

Alisertib + Paclitaxel

Placebo + Paclitaxel

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Dose Expansion: Cohort CExperimental Treatment2 Interventions

Stage IV EGFR-mutant NSCLC patients with no known tumor non-synonymous TP53 genomic alteration who are currently receiving first line osimertinib treatment and have received at least 3 months, but no more than 6 months, of osimertinib with a best response of PR or SD. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity.

Group II: Dose Expansion: Cohort BExperimental Treatment2 Interventions

Stage IV EGFR-mutant NSCLC patients who are currently receiving first line osimertinib treatment and have received at least 3 months, but no more than 6 months, of osimertinib with a best response of PR or SD. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity.

Group III: Dose Expansion: Cohort AExperimental Treatment2 Interventions

Stage IV EGFR-mutant NSCLC currently receiving and progressing on osimertinib who have received no more than one additional line of systemic cancer therapy other than osimertinib (e.g., chemotherapy +/- immunotherapy, amivantamab +/- Lazertinib) for metastatic disease. Patients may receive alisertib therapy until lack of clinical benefit or intolerable toxicity.

Group IV: Dose Escalation (Closed to Enrollment)Experimental Treatment2 Interventions

Patients will continue to receive osimertinib 80 mg PO daily as part of standard of care therapy during screening and study treatments. Alisertib will be administered to eligible patients in combination with osimertinib at doses ranging from 20 mg to 50 mg PO twice daily on days 1-3, 8-10, and 15-17 of a 28-day cycle. The starting alisertib dose will be 30 mg twice daily (dose level 1). All patients at a given dose level must complete the DLT period before any additional cohorts can be opened.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Osimertinib

2017

Completed Phase 4

~1120

Alisertib

2010

Completed Phase 2

~1260