Erlotinib and Standard Platinum-Based Chemotherapy for Newly Diagnosed, Advanced Non-Small Cell Carcinoma of the Lung

INST 0601C: A Non-Randomized Phase II Protocol of Erlotinib for Patients With Newly Diagnosed, Advanced Non-Small Cell Carcinoma of the Lung

This study was conducted to compare the activities of erlotinib to that of intravenous, platinum-based therapy in the treatment of non-small cell lung cancer (NSCLC). The goal of this trial was to demonstrate clinical equivalence of erlotinib to platinum-based frontline therapy, compared to historical controls.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Erlotinib; Drug: Platinum-based chemotherapy

Detailed Description

To compare the activities (the progression-free survival, the incidence and severity of toxicities, and reversibility of toxicities) of erlotinib to that of platinum-based therapy in NSCLC. A sequential therapy design has been chosen such that all patients will receive any potential benefits of both platinum-based and erlotinib therapy, without compromising survival by denying anyone potential therapy. With this design, progression-free survival will be tracked by treatment received. However, data will be generated which will show the safety and efficacy of erlotinib in the frontline setting (alone and with historical comparison to platinum-based therapy), as well as the potential safety and activity of platinum-based therapy in the "second-line" (post-erlotinib) setting. This should allow for the demonstration of the relative median time to progression, objective response and clinical benefit rates, overall survival, and safety and tolerability of erlotinib and platinum-based therapy in both the frontline and second-line settings in NSCLC. Also, in this fashion, the treatments serve as controls for each other, as well as being compared to historical controls; in the first line treatment portion, the platinum-based regimens serve as the historical control, while in the second-line setting, erlotinib serves as the historical control arm.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87110
      • Presbyterian Medical Group
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Group
    • Albuquerque, New Mexico, United States, 87106
      • Hematology Oncology Associates NM
    • Santa Fe, New Mexico, United States, 87505
      • New Mexico Cancer Care Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior chemotherapy will be allowed for other invasive malignancies, provided at least five years has elapsed since the completion of therapy and enrollment on this protocol. No prior chemotherapy for metastatic non-small cell lung cancer (NSCLC) will be allowed. Prior adjuvant or neoadjuvant chemotherapy for NSCLC will be allowed, provided at least six months have elapsed from the last dose of chemotherapy to the documentation of relapsed disease.

Baseline laboratory values (bone marrow, renal, hepatic):

• Adequate bone marrow function:

  • Absolute neutrophil count >1000/µL
  • Platelet count >100'000/µL

• Renal function:

  • Serum creatinine < 2.0 mg %

• Hepatic function:

  • Bilirubin <1.5x normal
  • Serum calcium < 12 mg/dl

Other Eligibility Criteria:

• Signed Informed Consent
• Eastern Cooperative Oncology Group (ECOG)/Zubrod/Southwest Oncology Group (SWOG) Performance Status <2 (Karnofsky Performance Status > 70%)
• Life expectancy > 8 weeks
• Male or female' age >18 years
• Patients of childbearing potential must be using an effective means of contraception.
• Histologic diagnosis of NSCLC that is advanced and cannot be treated adequately by radiotherapy or surgery; or metastatic disease

Exclusion Criteria:

• Prior therapy with an epidermal growth factor receptor inhibitor, including erlotinib, gefitinib, and cetuximab, as well as any investigational HER-1 inhibiting agent
• Pregnant or lactating females
• Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0
• Uncontrolled' clinically significant dysrhythmia
• History of prior malignancy within the prior five years, with the exception of non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix
• Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor growth in that lesion
• Uncontrolled metastatic disease of the central nervous system (previously treated, stable disease is allowable on this protocol)
• Radiotherapy within the 2 weeks before Cycle 1' Day 1
• Surgery within the 2 weeks before Cycle 1' Day 1
• Any co morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Erlotinib followed by chemotherapy; Erlotinib: 150 mg orally once daily, Platinum-based chemotherapy regimen selections include: Carboplatin (Carbo) area under the curve (AUC) 6, or cisplatin (Cis) 60-100 mg/m2, day (D)1, administered with one of the following: Docetaxel 75 mg/m2, D1; Docetaxel 35 mg/m2, D1,8,15; Paclitaxel 200-225 mg/m2, D1; Paclitaxel 80-100 mg/m2, D1,8,15 Carbo AUC 5-6, or Cis 60-100 mg/m2, D1, administered with one of the following: Etoposide 100 mg/m2 D1-3; Etoposide 200 mg/m2 orally D1-3; Pemetrexed 500 mg/m2, D 1; Irinotecan 50 mg/m2 D1,8,15 Other regimens: Gemcitabine 1000 mg/m2-1250 mg/m2, D1,8 + Carbo AUC 6, or Cis 60-100 mg/m2, D1 or 8; Vinorelbine 25 mg/m2 D1,8 + Carbo AUC 5, or Cis 80 mg/m2 D1

Drug: Erlotinib; Erlotinib will be administered for at least 2 cycles (6 weeks) and for a maximum of 8 months. Upon progression or intolerance to erlotinib, standard of care platinum-based chemotherapy (per the choice of the treating physician) is administered every 3 weeks. Physicians can adjust dose, schedule, or supportive care to the benefit of the patient; Other Names: Tarceva; OSI-774; Drug: Platinum-based chemotherapy; Intravenous chemotherapy combination per physician discretion every 3 weeks for at least 2 cycles; Other Names: paclitaxel + platinum; docetaxel + platinum; vinorelbine + platinum; pemetrexed + platinum; irinotecan + platinum; etoposide + platinum; gemcitabine + platinum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)		5 years
Toxicity Profile	Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Toxicities are reported as the number of patients who experienced grade 3 or grade 4 adverse events after receiving at least one dose of on-study treatment.	28 days after last on-study treatment

Collaborators and Investigators

• Sponsor: New Mexico Cancer Care Alliance
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Dennie V Jones, MD, University of New Mexico

Publications and helpful links

Helpful Links

• UNM CRTC Homepage

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: October 23, 2006
• First Submitted That Met QC Criteria: October 23, 2006
• First Posted (Estimate): October 24, 2006

Study Record Updates

• Last Update Posted (Estimate): August 17, 2015
• Last Update Submitted That Met QC Criteria: August 14, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: chemotherapy; lung; NSCLC; lung cancer; erlotinib; platinum
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Protein Kinase Inhibitors; Topoisomerase I Inhibitors; Folic Acid Antagonists; Gemcitabine; Docetaxel; Etoposide; Paclitaxel; Erlotinib Hydrochloride; Irinotecan; Vinorelbine; Pemetrexed
• Other Study ID Numbers: INST 0601C; NCI-2012-01264 (Registry Identifier: NCI CTRP)