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

NCT01998126 | Completed Phase 1 DMC

• 1 other identifier: HCI66705
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  36 months

Secondary Outcomes (4)

• Response rate

  36 months

• Progression Free Survival (PFS)

  36 months

• Overall Survival

  36 months

• immune function pre and post immune therapy

  36 months

Study Arms (4)

EGFR patients with ipilimumab

EXPERIMENTAL

ipilimumab and erlotinib in EGFR mutated patients

Drug: Ipilimumab; Drug: Erlotinib

ALK patients plus ipilimumab

EXPERIMENTAL

ipilimumab and crizotinib in ALK mutated patients

Drug: Ipilimumab; Drug: Crizotinib

EGFR patients with nivolumab

EXPERIMENTAL

nivolumab and erlotinib in EGFR mutated patients

Drug: Erlotinib; Drug: Nivolumab

ALK patients plus nivolumab

EXPERIMENTAL

nivolumab and crizotinib in ALK mutated patients

Drug: Crizotinib; Drug: Nivolumab

Interventions

Ipilimumab DRUG

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

Also known as: Yervoy

ALK patients plus ipilimumab; EGFR patients with ipilimumab

Erlotinib DRUG

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

EGFR patients with ipilimumab; EGFR patients with nivolumab

Crizotinib DRUG

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

ALK patients plus ipilimumab; ALK patients plus nivolumab

Nivolumab DRUG

Also known as: Nivolumab 240 mg every 2 weeks

ALK patients plus nivolumab; EGFR patients with nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• 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.

  PMID: 31346927 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; Erlotinib Hydrochloride; Crizotinib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Aminopyridines; Pyridines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2013
• First Posted: November 28, 2013
• Study Start: December 2, 2013
• Primary Completion: May 9, 2017
• Study Completion: March 29, 2018
• Last Updated: April 2, 2018

Record last verified: 2018-03

Locations

US (1)