TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02186301
First received: June 30, 2014
Last updated: February 16, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to compare the safety and anti-tumor effect of rociletinib with erlotinib in patients whose tumors have specific EGFR mutations and who have not previously received any treatment for advanced/metastatic EGFR mutated NSCLC. This study is a 'Randomized' Study. This means that upon entering the study, patients will be randomly assigned to be dosed with either rociletinib twice a day or erlotinib once a day. Patients will continue to take either rociletinib or erlotinib until it is no longer beneficial.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Rociletinib Mono-Therapy
Drug: Erlotinib Mono-Therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: TIGER 1: A Randomized, Open-Label, Phase 2/3 Study of CO-1686 or Erlotinib as First-Line Treatment of Patients With EGFR-Mutant Advanced/Metastatic NSCLC

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) according to RECIST Version 1.1 as determined by investigator review (invPFS) [ Time Frame: Cycle 1 Day 1 to End of Treatment, up to approximately 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • invPFS in patients with baseline T790M mutations detected in tumor using local screening EGFR mutation assay [ Time Frame: Cycle 1 Day 1 to End of Treatment, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Change from baseline in patient reported outcomes using the EORTC Quality of Life Questionnaire following treatment [ Time Frame: Every 4-12 weeks until disease progression, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Change from baseline in patient reported outcomes using the EORTC Quality of Life Questionnaire Lung Cancer module following treatment [ Time Frame: Every 4-12 weeks until disease progression, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Change from baseline in patient reported outcomes using the Dermatology Life Quality Index following treatment [ Time Frame: Every 4-12 weeks until disease progression, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Change from baseline in patient reported outcomes using the EQ-5D instrument following treatment [ Time Frame: Every 4-12 weeks until disease progression, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Treatment emergent adverse events (AEs), laboratory abnormalities and electrocardiogram (ECG) abnormalities [ Time Frame: Every 4 weeks until treatment discontinuation, up to approximately 24 months ] [ Designated as safety issue: Yes ]
  • Plasma PK parameters for rociletinib based on sparse sampling [ Time Frame: Every 4 weeks for approximately 6 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Cycle 1 Day 1 to Patient Date of Death, up to approximately 60 months ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) according to RECIST 1.1 as determined by investigator review [ Time Frame: Cycle 1 Day 1 to End of Treatment, up to approximately 24 months ] [ Designated as safety issue: No ]
  • Duration of Response (DR) according to RECIST 1.1 as determined by investigator review [ Time Frame: Cycle 1 Day 1 to End of Treatment, up to approximately 24 months ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: November 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Erlotinib Mono-Therapy Drug: Erlotinib Mono-Therapy
Erlotinib will be administered once a day
Experimental: Rociletinib Mono-Therapy Drug: Rociletinib Mono-Therapy
Rociletinib will be administered twice daily

Detailed Description:
This is a randomized, Phase 2/3 study of rociletinib versus erlotinib as a first-line treatment for patients with EGFR-mutant advanced/metastatic NSCLC whose tumors have EGFR-activating mutations. The study will consist of Phase 2 and Phase 3 parts which will use the same enrollment criteria and treatment assignment principles. Patients will be randomized 1:1 to erlotinib or rociletinib. The Phase 2 part is an open-label study. In the Phase 3 part, the sponsor will be blinded to the efficacy and safety results. The study will consist of a screening phase to establish study eligibility (including tumor genotype) and document baseline measurements, a treatment phase, in which patients will receive either rociletinib BID or erlotinib QD to ascertain safety and efficacy until protocol-defined disease progression, and a follow-up phase, to monitor survival status and subsequent NCSLC cancer therapy. In the Phase 2 part only, patients initially randomized to erlotinib may be eligible to participate in an optional crossover phase to receive rociletinib if they demonstrate the T790M resistance mutation after radiographic progression on erlotinib treatment among other eligibility requirements. Patients eligible for this study must have EGFR-mutated NSCLC who have not been treated with an EGFR-directed therapy.Treatment with rociletinib or erlotinib is continuous. Each 28 day period of treatment will represent one cycle, with dosing initiated on Cycle 1 Day 1 (C1 D1).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed metastatic or unresectable locally advanced/metastatic NSCLC
  2. Documented evidence of a tumor with activating EGFR mutations by local testing. Patients with exon 20 insertions are not eligible with the exception of patients with documented evidence of the exon 20 insertion A763_Y764insFQEA in the EGFR gene
  3. Have undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of the first day of study treatment, C1D1, and have tissue available to send to sponsor laboratories or are able to undergo a biopsy during screening and provide tissue to sponsor laboratories
  4. Measureable disease according to RECIST Version 1.1
  5. Life expectancy of at least 3 months
  6. ECOG performance status of 0 to 1
  7. Minimum age 18 years (in certain territories, the minimum age requirement may be higher (e.g. 20 years in Japan and Taiwan)
  8. Adequate hematological and biological function, confirmed by defined laboratory values
  9. Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation

Exclusion Criteria:

  1. Documented evidence of an exon 20 insertion activating mutation other than A763_Y764insFQEA in the EGFR gene
  2. Prior treatment with cytotoxic chemotherapy for advanced NSCLC; neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months has elapsed between the end of chemotherapy and randomization
  3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment
  4. Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to enroll in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant > 2 years prior to first day of study treatment
  5. Known pre-existing interstitial lung disease
  6. Brain metastases
  7. Treatment with prohibited medications less than or equal to 14 days prior to first day of study treatment
  8. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval if that treatment cannot be either discontinued or switched to a different medication prior to administration of study drug
  9. Prior treatment with EGFR TKIs (e.g. erlotinib, gefitinib, neratinib, afatinib, AZD9291, or dacomitinib), rociletinib or other drugs that target mutant EGFR
  10. Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) > 450 ms
  11. Inability to measure QT interval on ECG
  12. Personal or family history of long QT syndrome
  13. Implantable pacemaker or implantable cardioverter defibrillator
  14. Resting bradycardia < 55 beats/min
  15. Non-study related surgical procedures less than or equal to 7 days prior to administration of study drug. In all cases, the patient must be sufficiently recovered and stable before treatment administration.
  16. Females who are pregnant or breastfeeding
  17. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib and 2 weeks after the last dose of erlotinib
  18. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
  19. Any other reason the investigator considers the patient should not participate in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02186301

  Show 65 Study Locations
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

Additional Information:
Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02186301     History of Changes
Other Study ID Numbers: CO-1686-022 (TIGER-1) 
Study First Received: June 30, 2014
Last Updated: February 16, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Clovis Oncology, Inc.:
cancer
metastatic
locally advanced
lung
non-small cell lung cancer
NSCLC
epidermal growth factor receptor
EGFR
T790M
CO-1686
unresectable
recurrent
EGFR-directed therapy
irreversible EGFR inhibitor
TIGER
rociletinib

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016