NCT01822496

Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer

Terminated Phase 2 Results posted Last updated 5 August 2019

What this trial tests

Phase 2 trial testing Radiation Therapy in Stage III Non-Small Cell Lung Cancer AJCC v7 in 59 participants. Terminated before completion.

Timeline

4 November 2013

Primary endpoint
4 June 2018

4 June 2018

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	59
Start date	4 November 2013
Primary completion	4 June 2018
Estimated completion	4 June 2018
Sites	174 locations across United States

Drugs / interventions tested

• Radiation Therapy
• Carboplatin (Carboplatin) — full drug profile →
• Cisplatin (cisplatin) — full drug profile →
• Crizotinib (crizotinib) — full drug profile →
• Erlotinib
• Etoposide
• Paclitaxel — full drug profile →

Conditions studied

• Stage III Non-Small Cell Lung Cancer AJCC v7 — all drugs for Stage III Non-Small Cell Lung Cancer AJCC v7 →
• Stage IIIA Non-Small Cell Lung Cancer AJCC v7 — all drugs for Stage IIIA Non-Small Cell Lung Cancer AJCC v7 →
• Stage IIIB Non-Small Cell Lung Cancer AJCC v7 — all drugs for Stage IIIB Non-Small Cell Lung Cancer AJCC v7 →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Stage III Non-Small Cell Lung Cancer AJCC v7 or Stage IIIA Non-Small Cell Lung Cancer AJCC v7. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival Primary · From randomization to study termination. Maximum follow-up was 39.0 months

Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions at any location. Progression-free survival time is measured from the date of randomization to the date of first progression, death, or last known follow-up (censored). No statistical testing was done due to early study termination.

Group	Value	95% CI
EGFR: Erlotinib	21.1	8.5 – NA
EGFR: No Erlotinib	9.2	8.7 – NA
ALK: Crizotinib	14.7	6.4 – 19.5
ALK: No Crizotinib	NA	NA – NA

Percentage of Patients With Complete or Partial Response Secondary · From randomization to study termination. Maximum follow-up was 39.0 months

Per the RECIST guideline v1.1 complete response is defined as the disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. No statistical testing was done due to early study termination.

Group	Value	95% CI
EGFR: Erlotinib	50.0	19.0 – 81.0
EGFR: No Erlotinib	26.7	4.3 – 49.1
ALK: Crizotinib	66.7	29.0 – 100.0
ALK: No Crizotinib	75.0	32.6 – 100.0

Number of Patients With Grade 3-5 Adverse Events Secondary · From randomization to study termination. Maximum follow-up was 39.0 months

Adverse events (AE) are graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Group	Value	95% CI
EGFR: Erlotinib	0
EGFR: No Erlotinib	0
ALK: Crizotinib	0
ALK: No Crizotinib	0

Overall Survival Secondary · From randomization to study termination. Maximum follow-up was 39.0 months

Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

Group	Value	95% CI
EGFR: Erlotinib	NA	NA – NA
EGFR: No Erlotinib	35.9	35.9 – NA
ALK: Crizotinib	NA	NA – NA
ALK: No Crizotinib	NA	NA – NA

Local-regional Progression-free Survival Secondary · From randomization to study termination. Maximum follow-up was 39.0 months

Progression is defined using the RECIST guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new regional lesions. Local progression is defined as progression within the planning target volume (PTV). Regional progression is defined as progression outside of the PTV but within the same lobe of the lung as the primary tumor or in regional lymph nodes as defined by the American Joint Committee on Cancer (AJCC) 7th edition nodal stations. Local-regional progression-free survival time is measured

Group	Value	95% CI
EGFR: Erlotinib	25.7	8.5 – NA
EGFR: No Erlotinib	NA	NA – NA
ALK: Crizotinib	14.7	6.4 – 19.5
ALK: No Crizotinib	NA	NA – NA

Distant Progression-free Survival Secondary · From randomization to study termination. Maximum follow-up was 39.0 months

Distant progression is defined as the first occurrence of distant metastasis. Distant progression-free survival time is measured from the date of randomization to the date of first distant progression, death, or last known follow-up (censored). Distant progression-free survival rates are estimated using the Kaplan-Meier method. No testing was done due to early study termination.

Group	Value	95% CI
EGFR: Erlotinib	NA	NA – NA
EGFR: No Erlotinib	35.9	8.9 – 35.9
ALK: Crizotinib	NA	NA – NA
ALK: No Crizotinib	20.1	7.8 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization to last follow-up. Maximum follow-up was 39.0 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

EGFR: Erlotinib

Serious: 1/14 (7%)

Deaths: 1/14

EGFR: No Erlotinib

Serious: 7/20 (35%)

Deaths: 3/20

ALK: Crizotinib

Serious: 4/9 (44%)

Deaths: 2/9

ALK: No Crizotinib

Serious: 2/7 (29%)

Deaths: 1/7

Serious adverse events (28 terms)

Reaction	System	EGFR: Erlotinib	EGFR: No Erlotinib	ALK: Crizotinib	ALK: No Crizotinib
Vomiting	Gastrointestinal disorders	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Esophageal fistula	Gastrointestinal disorders	—	—	—	—
Esophageal stenosis	Gastrointestinal disorders	—	—	—	—
Esophagitis	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Fever	General disorders	—	—	—	—
General disorders and administration site conditions - Other	General disorders	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Weight loss	Investigations	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—	—	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—
Delirium	Psychiatric disorders	—	—	—	—
Aspiration	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (174 terms — click to expand)

Reaction	System	EGFR: Erlotinib	EGFR: No Erlotinib	ALK: Crizotinib	ALK: No Crizotinib
Nausea	Gastrointestinal disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Esophagitis	Gastrointestinal disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—
Dermatitis radiation	Injury, poisoning and procedural complications	—	—	—	—
Rash acneiform	Skin and subcutaneous tissue disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
White blood cell decreased	Investigations	—	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Fever	General disorders	—	—	—	—
Creatinine increased	Investigations	—	—	—	—
Weight loss	Investigations	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Edema limbs	General disorders	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Vomiting, Lung infection, Atrial fibrillation, Diarrhea, Esophageal fistula, Esophageal stenosis, Esophagitis, Fatigue.

Data from ClinicalTrials.gov NCT01822496 adverse events section.

Sponsor's own description

This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with chemoradiation therapy works in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeted therapy in cancer.
   Tsimberidou AM. · · 2015 · cited 156× · PMID 26391154 · DOI 10.1007/s00280-015-2861-1
2. c-Met as a Target for Personalized Therapy.
   Garajová I, Giovannetti E, Biasco G, Peters GJ. · · 2015 · cited 106× · PMID 26628860 · DOI 10.4137/tog.s30534
3. Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy.
   Aredo JV, Mambetsariev I, Hellyer JA, Amini A, et al · · 2021 · cited 101× · PMID 33588109 · DOI 10.1016/j.jtho.2021.01.1628
4. Novel radiotherapy approaches for lung cancer: combining radiation therapy with targeted and immunotherapies.
   Simone CB, Burri SH, Heinzerling JH. · · 2015 · cited 70× · PMID 26629423 · DOI 10.3978/j.issn.2218-6751.2015.10.05
5. Patient-Specific Tumor Growth Trajectories Determine Persistent and Resistant Cancer Cell Populations during Treatment with Targeted Therapies.
   Grassberger C, McClatchy D, Geng C, Kamran SC, et al · · 2019 · cited 33× · PMID 31113818 · DOI 10.1158/0008-5472.can-18-3652
6. Early-stage anaplastic lymphoma kinase (<i>ALK</i>)-positive lung cancer: a narrative review.
   Chen MF, Chaft JE. · · 2023 · cited 23× · PMID 36895922 · DOI 10.21037/tlcr-22-631
7. Time dependent modulation of tumor radiosensitivity by a pan HDAC inhibitor: abexinostat.
   Rivera S, Leteur C, Mégnin F, Law F, et al · · 2017 · cited 14× · PMID 28915585 · DOI 10.18632/oncotarget.14813
8. Perspective on treatment for unresectable locally advanced non-small cell lung cancer with oncogene-driven mutation: a narrative review.
   Jiang L, Meng X, Zhao X, Xing L, et al · · 2020 · cited 9× · PMID 33209632 · DOI 10.21037/tlcr-20-722