Non-small Cell Lung CancerPhase 1NCT01998126
Combination Checkpoint Inhibitor Plus Erlotinib or Crizotinib for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer
A Phase 1 study testing Ipilimumab, Erlotinib and Crizotinib in people with Non-small Cell Lung Cancer, run by University of Utah at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Ipilimumab, Erlotinib and Crizotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Dec 2013to 29 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: Evaluation of Combination Checkpoint Inhibitor Plus Targeted Inhibitor (Erlotinib or Crizotinib) for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer: Phase Ib With Expansion Cohorts
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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Ipilimumab, Erlotinib, Crizotinib, Nivolumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Ipilimumab 3 mg/kg x 4 (given with standard Erlotinib or Crizotinib based on mutation)
ErlotinibDrug
Erlotinib 150 mg once daily or current tolerable dose (given with Ipilimumab)
CrizotinibDrug
Crizotinib 250 mg twice daily or current tolerable dose (given with Ipilimumab)
NivolumabDrug
Also called Nivolumab 240 mg every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| EGFR patients with ipilimumab | Experimental | ipilimumab and erlotinib in EGFR mutated patients Receives: Drug: Ipilimumab; Drug: Erlotinib |
| ALK patients plus ipilimumab | Experimental | ipilimumab and crizotinib in ALK mutated patients Receives: Drug: Ipilimumab; Drug: Crizotinib |
| EGFR patients with nivolumab | Experimental | nivolumab and erlotinib in EGFR mutated patients Receives: Drug: Erlotinib; Drug: Nivolumab |
| ALK patients plus nivolumab | Experimental | nivolumab and crizotinib in ALK mutated patients Receives: Drug: Crizotinib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 36 months
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.
Measured: 36 months
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.
Measured: 36 months
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.
Measured: 36 months
Secondary outcomes (4)
Response rate
Measured: 36 months
Progression Free Survival (PFS)
Measured: 36 months
Overall Survival
Measured: 36 months
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.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2013 (estimated)
- Study start2 Dec 2013
- Primary completion9 May 2017
- Study completion29 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01998126
- Sponsor's protocol ID
- HCI66705
- Status last verified
- Mar 2018
- First submitted
- 11 Jul 2013
- Last updated
- 2 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
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
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Combination Checkpoint Inhibitor Plus Targeted Inhibitor (Erlotinib or Crizotinib) for EGFR or ALK Mutated Stage IV Non-small Cell Lung Cancer: Phase Ib With Expansion Cohorts
- ClinicalTrials.gov ID
- NCT01998126
- Acronym / sponsor ID
- HCI66705
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 2 Dec 2013 (actual)
- Primary completion
- 9 May 2017 (actual)
- Study completion
- 29 Mar 2018 (actual)
- First posted
- 28 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| EGFR patients with ipilimumab | Experimental | Drug: Ipilimumab, Drug: Erlotinibipilimumab and erlotinib in EGFR mutated patients |
| ALK patients plus ipilimumab | Experimental | Drug: Ipilimumab, Drug: Crizotinibipilimumab and crizotinib in ALK mutated patients |
| EGFR patients with nivolumab | Experimental | Drug: Erlotinib, Drug: Nivolumabnivolumab and erlotinib in EGFR mutated patients |
| ALK patients plus nivolumab | Experimental | Drug: Crizotinib, Drug: Nivolumabnivolumab and crizotinib in ALK mutated patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (16 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IpilimumabAlso: YervoyIpilimumab 3 mg/kg x 4 (given with standard Erlotinib or Crizotinib based on mutation) | Drug | ALK patients plus ipilimumab, EGFR patients with ipilimumab |
| ErlotinibErlotinib 150 mg once daily or current tolerable dose (given with Ipilimumab) | Drug | EGFR patients with ipilimumab, EGFR patients with nivolumab |
| CrizotinibCrizotinib 250 mg twice daily or current tolerable dose (given with Ipilimumab) | Drug | ALK patients plus ipilimumab, ALK patients plus nivolumab |
| NivolumabAlso: Nivolumab 240 mg every 2 weeks | Drug | ALK patients plus nivolumab, EGFR patients with nivolumab |
Primary outcome
toxicity of ipilimumab and erlotinib in EGFR mutated patients
Time frame: 36 months
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.
toxicity of ipilimumab and crizotinib in ALK mutated patients
Time frame: 36 months
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.
toxicity of nivolumab and erlotinib in EGFR mutated patients
Time frame: 36 months
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.
toxicity of nivolumab and crizotinib in ALK mutated patients
Time frame: 36 months
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.
4 secondary outcomes
Response rate
Time frame: 36 months
Progression Free Survival (PFS)
Time frame: 36 months
Overall Survival
Time frame: 36 months
immune function pre and post immune therapy
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2018.
- Derived from this study: PubMed 31346927Chalmers 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab, Erlotinib and Crizotinib in people with Non-small Cell Lung Cancer, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
toxicity of ipilimumab and erlotinib in EGFR mutated patients (time frame: 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01998126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2018.