Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients

NCT01526928 | Terminated Phase 1 Results

• 1 other identifier: CO-1686-008
• Study Type: interventional
• Target: 612
• Locations: 4 countries
• Sites: 49

Brief Summary

Rociletinib is a novel, potent, small molecule irreversible tyrosine kinase inhibitor (TKI) that selectively targets mutant forms of the epidermal growth factor receptor (EGFR) while sparing wild-type (WT) EGFR. The purpose of the study is to evaluate the pharmacokinetic (PK) and safety profile of oral rociletinib; to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of oral rociletinib; to assess the safety and efficacy of rociletinib in previously treated NSCLC patients known to have the T790M EGFR mutation.

Conditions

Locally Advanced or Metastatic Non Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Percentage of T790M Positive Patients With Confirmed Response Per Investigator

  Percentage of patients with a T790M mutation (determined by central lab) with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is 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 (PR),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

  Cycle 1 Day 1 to End of Treatment, up to approximately 42 months

• Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment

  Duration of Response in patients with a T790M mutation (determined by central lab) with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from the date that any of these best responses is first recorded until the first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis.

  Cycle 1 Day 1 to End of Treatment, up to approximately 36 months

• Dose Limiting Toxicity (DLT) Incidence

  The number of Phase 1 patients who experienced dose limiting toxicities after one cycle (21 days) of study drug.

  Cycle 1 Day 1 to Cycle 1 Day 21

Secondary Outcomes (14)

• Overall Survival (OS) Determined by Investigator Assessment

  Cycle 1 Day 1 to date of death, assessed up to 42 months

• Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)

  Cycle 1 Day 1 to End of Treatment, up to approximately 42 months

• PK Profile of Rociletinib - Cmax

  Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

• PK Profile of Rociletinib - Tmax

  Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

• PK Profile of Rociletinib - AUC 0-24

  Cycle 1 Day 1 to Cycle 1 Day 15, or approximately 15 days

Study Arms (6)

Rociletinib <900 mg BID FB formulation

EXPERIMENTAL

Rociletinib free base (FB) dose \<900 mg twice a day (BID)

Drug: Rociletinib

Rociletinib 900 mg BID FB formulation

EXPERIMENTAL

Rociletinib free base (FB) dose 900 mg twice a day (BID)

Drug: Rociletinib

Rociletinib 500 mg BID HBr formulation

EXPERIMENTAL

Rociletinib hydrobromide (HBr) dose 500 mg twice a day (BID)

Drug: Rociletinib

Rociletinib 625 mg BID HBr formulation

EXPERIMENTAL

Rociletinib hydrobromide (HBr) dose 625 mg twice a day (BID)

Drug: Rociletinib

Rociletinib 750 mg BID HBr formulation

EXPERIMENTAL

Rociletinib hydrobromide (HBr) dose 750 mg twice a day (BID)

Drug: Rociletinib

Rociletinib 1000 mg BID HBr formulation

EXPERIMENTAL

Rociletinib hydrobromide (HBr) dose 1000 mg twice a day (BID)

Drug: Rociletinib

Interventions

Rociletinib DRUG

Phase 1: Rociletinib \<900 mg BID FB will be administered in escalating dosages in a period of 21-day cycles

Also known as: CO-1686

Rociletinib <900 mg BID FB formulation

Eligibility Criteria

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

You may qualify if:

• Metastatic or unresectable locally advanced NSCLC
• Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion
• Biopsy of either primary or metastatic tumor tissue within 60 days of dosing
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Minimum age of 18 years
• Adequate hematological and biological function
• Written consent on an IRB/IEC-approved Informed Consent Form (ICF) prior to any study-specific evaluation
• Disease progression confirmed by radiologic assessment while on treatment with EGFR- TKI Or
• Disease progression confirmed by radiologic assessment while on treatment with the first single agent EGFR TKI and
• Documented evidence of T790M mutation in EGFR following disease progression on the first single agent EGFR TKI.
• Measureable disease according to RECIST Version 1.1

You may not qualify if:

• Any of the following criteria will exclude patients from study participation:
• Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene
• Active second malignancy
• Known pre-existing interstitial lung disease
• Patients with Leptomeningeal carcinomatosis are excluded. Other CNS metastases are only permitted if treated, asymptomatic and stable (not requiring steroids for at least 4 weeks prior to start of study treatment).
• Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication before starting rociletinib
• Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR
• Certain cardiac abnormalities or history
• Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib
• Females who are pregnant or breastfeeding
• Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib
• Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study
• Any other reason the investigator considers the patient should not participate in the study

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead

Study Sites (49)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Compassionate Care Research Group, Inc.

Fountain Valley, California, 92708, United States

Location

University of Southern California, Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Samuel Oschin Cancer Center

Los Angeles, California, 90048, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

UCLA Health System

Santa Monica, California, 90404, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

East Valley Hematology and Oncology Medical Group, Inc.

Whittier, California, 90603, United States

Location

The Oncology Institute of Hope and Innovations

Whittier, California, 90603, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, 33136, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

University Cancer & Blood Center

Athens, Georgia, 30607, United States

Location

University of Chicago Medical Center, The Duchossois Center for Advanced Medicine

Chicago, Illinois, 60637, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106-0995, United States

Location

Karmanos Cancer Care Institute

Detroit, Michigan, 48201, United States

Location

Regional Cancer Care Associates

Morristown, New Jersey, 07962, United States

Location

Regional Cancer Center

New Brunswick, New Jersey, 07834, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State University, Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

Location

Tulsa Cancer Institute

Tulsa, Oklahoma, 74146, United States

Location

Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland

Portland, Oregon, 97213, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Cancer Institute (UPMC), Div. of Medical Oncology

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9179, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Australia

Location

Centre Hospitalier Universitaire de Grenoble

Grenoble, Auvergne-Rhône-Alpes, France

Location

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Location

Centre Antoine Lacassagne

Nice, Provence-Alpes-Côte d'Azur Region, 06189, France

Location

Centre François Baclesse

Caen, France

Location

Centre Hospitalier Intercommunal Créteil

Créteil, France

Location

Centre Hospitalier Régional Universitaire de Lille

Lille, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Med University Gdansk

Gdansk, Poland

Location

Related Publications (2)

• Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, Brinkmann K, Emenegger J, Grimm DG, Castellanos-Rizaldos E, Goldman JW, Sequist LV, Soria JC, Camidge DR, Gadgeel SM, Wakelee HA, Raponi M, Noerholm M, Skog J. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol. 2018 Mar 1;29(3):700-706. doi: 10.1093/annonc/mdx765.

  PMID: 29216356 DERIVED

• Sequist LV, Soria JC, Goldman JW, Wakelee HA, Gadgeel SM, Varga A, Papadimitrakopoulou V, Solomon BJ, Oxnard GR, Dziadziuszko R, Aisner DL, Doebele RC, Galasso C, Garon EB, Heist RS, Logan J, Neal JW, Mendenhall MA, Nichols S, Piotrowska Z, Wozniak AJ, Raponi M, Karlovich CA, Jaw-Tsai S, Isaacson J, Despain D, Matheny SL, Rolfe L, Allen AR, Camidge DR. Rociletinib in EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1700-9. doi: 10.1056/NEJMoa1413654.

  PMID: 25923550 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

rociletinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Results Point of Contact

• Title: Medical Information Department
• Organization: Clovis Oncology

medinfo@clovisoncology.com

+1 415 409 7220

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: February 6, 2012
• Study Start: March 27, 2012
• Primary Completion: July 3, 2018
• Study Completion: August 27, 2018
• Last Updated: August 4, 2020
• Results First Posted: January 6, 2020

Record last verified: 2020-07

Locations

PL (1); US (39); AU (2); FR (7)