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

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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 they started to nearby tissue or lymph nodes (locally advanced) or to other places in the body (metastatic) or stage IIIB-IV non-small cell lung cancer. Ceritinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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+