CClinicalTrials.gg
Sign In
CompletedNCT01998126Updated Apr 2, 2018

Combination Checkpoint Inhibitor Plus Erlotinib or Crizotinib for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer

A Phase 1 interventional study of Ipilimumab and Erlotinib in Non-small Cell Lung Cancer, sponsored by University of Utah. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-04-02.

Sponsored by University of Utah · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
14
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

The goals of the overall study are to evaluate a recommended phase 2 dose and the short and long term toxicities of the combinations. This is a modified phase I trial of immune checkpoint inhibitors in combination with mutation - specific targeted therapy (crizotinib or erlotinib) at conventional doses stratified for presence of ALK (Anaplastic lymphoma kinase) or EGFR (epidermal growth factor receptor) mutation.

The goals of the overall study are to evaluate a recommended phase 2 dose and the short and long term toxicities of the combinations.

02

Conditions studied

  • Non-small Cell Lung Cancer
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 14 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

University of Utah is the lead sponsor of 969 studies on the registry; 178 are open to participants now.

Of its 107 completed or terminated interventional studies of FDA-regulated products, 62 (58%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosis of Stage IV Non-Small Cell Lung Cancer (NSCLC), or Stages II - III NSCLC that cannot be treated curatively with standard techniques.
  • Non-Small Cell Lung Cancer (NSCLC) that is either EGFR or ALK mutated.
  • Untreated with/or actively treated with specific inhibitor for less than 6 months if not progressing on active therapy.
  • Age > 18.
  • ECOG performance status 0, 1 or 2.
  • Prior chemotherapy is allowed if > one month from the end of treatment. Patients must not have received chemotherapy within 4 weeks of the start of study drug.
  • Brain metastases are allowed if the patient is asymptomatic or previous steroid treatment was discontinued > 6 weeks.
  • Adequate bone marrow function as defined in the protocol
  • Serum bilirubin levels \< 1.5 mg/dL except for patients with Gilbert's syndrome.
  • Adequate organ function as defined in the protocol
  • If female and of childbearing potential, documentation of negative pregnancy test (serum or urine) within 7 days prior to first dose.
  • Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.

Exclusion criteria

Exclusion Criteria:

  • Concurrent therapy with any other non-protocol anti-cancer therapy.
  • History of any other malignancy requiring active treatment.
  • Patients who have had a history of acute diverticulitis, intra-abdominal abscess, Gastrointestical obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
  • History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome). History of vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are allowed.
  • Significant cardiovascular disease including:
  • Active, clinically symptomatic left ventricular failure.
  • Uncontrolled symptomatic hypertension that cannot be controlled with anti-hypertensive agents.
  • Myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug.
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
  • Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
  • Coronary or peripheral artery bypass graft within 6 months of screening.
  • Uncontrolled CNS metastases are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been treated, toxicities have resolved to grade 1 or baseline and steroids are no longer required. Leptomeningeal metastases are not allowed.
  • Serious/active infection or infection requiring parenteral antibiotics.
  • Pregnant or lactating females.
  • HIV infection or chronic hepatitis B or C. Negative Screening tests for HIV, Hepatitis B, and Hepatitis C are required.
  • The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    EGFR patients with ipilimumab

    ipilimumab and erlotinib in EGFR mutated patients

    Drug: Ipilimumab · Drug: Erlotinib

  • Experimental
    ALK patients plus ipilimumab

    ipilimumab and crizotinib in ALK mutated patients

    Drug: Ipilimumab · Drug: Crizotinib

  • Experimental
    EGFR patients with nivolumab

    nivolumab and erlotinib in EGFR mutated patients

    Drug: Erlotinib · Drug: Nivolumab

  • Experimental
    ALK patients plus nivolumab

    nivolumab and crizotinib in ALK mutated patients

    Drug: Crizotinib · Drug: Nivolumab

Interventions

  • DrugIpilimumab

    Ipilimumab 3 mg/kg x 4 (given with standard Erlotinib or Crizotinib based on mutation)

    Also known as: Yervoy

  • DrugErlotinib

    Erlotinib 150 mg once daily or current tolerable dose (given with Ipilimumab)

  • DrugCrizotinib

    Crizotinib 250 mg twice daily or current tolerable dose (given with Ipilimumab)

  • DrugNivolumab

    Also known as: Nivolumab 240 mg every 2 weeks

06

What researchers measure

Primary outcomes

  1. toxicity of ipilimumab and erlotinib in EGFR mutated patients

    The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.

    Time frame: 36 months

  2. toxicity of ipilimumab and crizotinib in ALK mutated patients

    The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.

    Time frame: 36 months

  3. toxicity of nivolumab and erlotinib in EGFR mutated patients

    The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.

    Time frame: 36 months

  4. toxicity of nivolumab and crizotinib in ALK mutated patients

    The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab/nivolumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease.

    Time frame: 36 months

Secondary outcomes

  1. Response rate

    Time frame: 36 months

  2. Progression Free Survival (PFS)

    Time frame: 36 months

  3. Overall Survival

    Time frame: 36 months

  4. immune function pre and post immune therapy

    The immune-related response criteria (irRC) incorporate several elements reflecting the complex tumor dynamics of ipilimumab treatment. Under these criteria, a measure of tumor volume is used that incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear. New lesions alone do not qualify as immune-related progressive disease. In this study, immune-related response criteria (irRC) will be used to assess subject response to study treatment per investigator assessment. The secondary endpoint irPFS will be determined based on investigator assessment. In order to adequately address this secondary objective, investigators will follow the clinical practice guidelines to obtain additional tumor assessments beyond mWHO PD and follow the instructions in this section for the determination of immune-related response.

    Time frame: 36 months

07

Study locations

1 site
  • Huntsman Cancer Institute
    Salt Lake City, Utah 84112, United States
08

References and documents

Publications

  • Chalmers AW, Patel S, Boucher K, Cannon L, Esplin M, Luckart J, Graves N, Van Duren T, Akerley W. Phase I Trial of Targeted EGFR or ALK Therapy with Ipilimumab in Metastatic NSCLC with Long-Term Follow-Up. Target Oncol. 2019 Aug;14(4):417-421. doi: 10.1007/s11523-019-00658-0. PubMed 31346927 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 2, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01998126
Lead sponsor
University of Utah
Collaborators
Bristol-Myers Squibb
Responsible party
Sponsor
First posted
Nov 28, 2013
Start date
Dec 2, 2013
Primary completion
May 9, 2017
Completion
Mar 29, 2018
Last update
Apr 2, 2018

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Lung Neoplasms→

Other studies from this sponsor

University of Utah

Start the discussion