Ceritinib + Everolimus for Lung Cancer

Overseen By George R. Blumenschein

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Lipid lowering

Must not be taking: QT prolonging, CYP3A4/5 inhibitors

Disqualifiers: Interstitial lung disease, Uncontrolled diabetes, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and observe the side effects of two drugs, ceritinib and everolimus, for treating advanced lung cancer. These drugs may inhibit cancer cell growth by blocking essential enzymes. People with stage IIIB or IV non-small cell lung cancer who have not responded to other treatments might be suitable candidates for this trial. Participants should be able to swallow pills and have tumors that can be biopsied for study purposes.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I have to stop taking my current medications to join the trial?

The trial requires you to stop taking certain medications, especially those that affect heart rhythm, certain enzymes, or are strong inhibitors or inducers of specific liver enzymes. You should discuss your current medications with the trial team to see if any need to be stopped or adjusted before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both ceritinib and everolimus have been studied for their safety in humans. Ceritinib has proven effective in treating certain types of lung cancer and sometimes outperforms crizotinib. However, like many cancer treatments, it can cause side effects. Patients have reported nausea, diarrhea, and liver problems, but these are often manageable.

The FDA has already approved everolimus for other conditions, so its safety is well-known. Common side effects include mouth sores, infections, and fatigue, but patients usually tolerate these well.

In studies where ceritinib and everolimus are used together, researchers aim to find the best doses to reduce side effects. This trial is in its early stages, focusing on balancing effectiveness and safety. Participants might experience some side effects, but careful monitoring will manage them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ceritinib and everolimus for lung cancer because these drugs offer a novel approach by combining targeted therapies. Ceritinib specifically inhibits a protein called ALK, which can drive cancer growth, while everolimus targets the mTOR pathway, an important route for cancer cell survival and proliferation. This dual-action strategy differs from traditional chemotherapy by potentially offering more precise and effective cancer control with fewer side effects.

What evidence suggests that ceritinib and everolimus might be effective treatments for lung cancer?

Research has shown that ceritinib effectively treats advanced non-small cell lung cancer (NSCLC), especially in patients with ALK-positive tumors. It outperforms crizotinib, another treatment option, by extending patient survival and slowing cancer progression. Ceritinib blocks specific enzymes that promote cancer cell growth. In this trial, participants will receive a combination of ceritinib and everolimus. Everolimus further inhibits the pathways cancer cells use to grow. Early studies suggest that this combination could be promising for treating advanced or metastatic NSCLC. ^{2 4 6 7 8}

Who Is on the Research Team?

George R Blumenschein

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or stage IIIB-IV non-small cell lung cancer that has spread and who have tried at least one therapy. They must have adequate blood counts, organ function, be able to swallow pills, not be pregnant or breastfeeding, use effective contraception if of childbearing potential, and not have severe medical conditions or a history of certain allergies.

Inclusion Criteria

My tumor can be sampled with a needle or biopsy for research.

I have stage IIIB or IV ALK+ NSCLC and my cancer is getting worse despite treatment with an ALK inhibitor.

Platelets >= 100,000/microliter

Exclusion Criteria

I am not currently on cancer treatment and haven't been for the last 4 weeks.

I am allergic to some ingredients in ceritinib medication.

Patients who have any severe and/or uncontrolled medical conditions such as: active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus test [hepatitis B virus (HBV)-deoxyribonucleic acid (DNA)] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus test [hepatitis C virus (HCV)-ribonucleic acid (RNA)], known severely impaired lung function (spirometry and carbon monoxide diffusing capacity [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air), active, bleeding diathesis, chronic treatment with high dose corticosteroids or other immunosuppressive agents; topical, inhaled, and low dose oral corticosteroids are allowed provided stable dosing for at least 2 weeks, receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with ceritinib and for the duration of the study participation: medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes, strong inhibitors or strong inducers of cytochrome P450, family 3, subfamily A, polypeptide 4/cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A4/5), medications with a low therapeutic index that are primarily metabolized by CYP3A4/5, cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) and/or cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), therapeutic doses of warfarin sodium (Coumadin) or any other Coumadin-derived anti-coagulant; anticoagulants not derived from warfarin are allowed (e.g., dabigatran, rivaroxaban, apixaban), unstable or increasing doses of corticosteroids, enzyme-inducing anticonvulsive agents, herbal supplements, known history of human immunodeficiency virus (HIV) seropositivity, patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines, patients who have a history of another primary malignancy unless the patient has been disease free for >= 3 years, patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study, patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing (except ALK inhibitors), pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test, women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment; highly effective contraception methods include: total abstinence (when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate; for female subjects on the study the vasectomized male partner should be the sole partner for that subject, combination of any two of the following: use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; in case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment; women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to screening; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential, sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment; male patients for 3 months should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid; also male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 3 months after the end of enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ceritinib and everolimus orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ceritinib
• Everolimus

Trial Overview The trial is testing the combination of two drugs: Ceritinib and Everolimus. These drugs are thought to block enzymes needed for tumor growth. The study aims to find the best dose with acceptable side effects for patients with locally advanced or metastatic solid tumors or specific stages of lung cancer.

How Is the Trial Designed?

Group I: Treatment (ceritinib, everolimus) Experimental Treatment 4 Interventions

Patients receive ceritinib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ceritinib is already approved in United States for the following indications:

Approved in United States as Danyelza for:

• High-risk neuroblastoma in the bone or bone marrow

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10416536/

Recent advances in non-small cell lung cancer targeted therapy A second-generation ALK inhibitor, ceritinib, has been demonstrated to successfully treat advanced or metastatic ALK-positive NSCLC, including in patients who ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1556086416305044

Comparative Efficacy of Ceritinib and Crizotinib as Initial ... Ceritinib was associated with prolonged OS and PFS compared with crizotinib when used as initial ALK-targeted therapy for previously treated ALK-positive NSCLC.

3. jto.org jto.org/article/S1556-0864(16)30504-4/pdf

Comparative Efficacy of Ceritinib and Crizotinib as Initial ... We compared efficacy outcomes between patients receiving ceritinib and an external control group receiving crizotinib, both as initial ALK- ...

4. cancerci.biomedcentral.com cancerci.biomedcentral.com/articles/10.1186/s12935-023-02990-y

Recent advances in non-small cell lung cancer targeted therapy Preclinical findings show that ceritinib is 20 times more effective against ALK than crizotinib. Additionally, it has been demonstrated that ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/everolimus?pn=1

Clinical Trials Using Everolimus - NCI Ceritinib and Everolimus in Treating Patients with Locally Advanced or Metastatic Solid Tumors or Stage IIIB-IV Non-small Cell Lung Cancer. Status ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02321501

Ceritinib and Everolimus in Treating Patients With Locally ... This phase I trial studies the side effects and best dose of ceritinib and everolimus in treating patients with solid tumors that have spread from where ...

7. clinconnect.io clinconnect.io/trials/NCT02321501

Ceritinib and Everolimus in Treating Patients With - ClinConnect This phase I trial studies the side effects and best dose of ceritinib and everolimus in treating patients with solid tumors that have spread from where ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26973324/

Activity and safety of ceritinib in patients with ALK-rearranged ... Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in vivo, and shows clinical responses in patients with ...