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

NCT ID: NCT01526928

Last Updated: 2020-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 612 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-27
• Study Completion Date: 2018-08-27

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.

Detailed Description

Lung cancer remains the most common cancer worldwide with non-small cell lung cancer accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs eventually progress, and in approximately 50% of cases, progression is due to development of an additional mutation called T790M. There are currently no approved therapies for patients who progress on TKIs. Rociletinib may provide an effective therapy for a patient population with few alternative treatment options. Nonclinical data demonstrate that rociletinib inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells with the T790M mutation, thus providing possible therapeutic benefit in patients who have developed T790M-mediated resistance to first generation TKIs.

This is a two-part, open-label study of oral rociletinib administered daily in previously treated NSCLC patients who have documented evidence of an activating mutation in the EGFR gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or afatinib.

This study will include 2 parts:

Phase 1: Dose-escalation Period with 21-day cycles; optional Treatment Extension Period starting on Day 22

Phase 2: Evaluation of activity and safety in patients with the T790M EGFR mutation who have:

Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR directed therapy received and also had no more than one previous line of chemotherapy or Cohort C - Patients with discordance between local (T790M positive) and central (T790M negative) T790M results, or had no central test result due to inadequacy of the tissue specimen and known to be T790M positive by local test

Conditions

Locally Advanced or Metastatic Non Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rociletinib <900 mg BID FB formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

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

Rociletinib 900 mg BID FB formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

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

Rociletinib 500 mg BID HBr formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Phase 1: Rociletinib 500 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 500 mg BID HBr will be administered daily

Rociletinib 625 mg BID HBr formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Phase 1: Rociletinib 625 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 625 mg BID HBr will be administered daily

Rociletinib 750 mg BID HBr formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Phase 1: Rociletinib 750 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 750 mg BID HBr will be administered daily

Rociletinib 1000 mg BID HBr formulation

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

Group Type: EXPERIMENTAL

Rociletinib

Intervention Type: DRUG

Phase 1: Rociletinib 1000 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 1000 mg BID HBr will be administered daily

Interventions

Rociletinib

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

Intervention Type: DRUG

Rociletinib

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

Intervention Type: DRUG

Rociletinib

Phase 1: Rociletinib 500 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 500 mg BID HBr will be administered daily

Intervention Type: DRUG

Rociletinib

Phase 1: Rociletinib 625 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 625 mg BID HBr will be administered daily

Intervention Type: DRUG

Rociletinib

Phase 1: Rociletinib 750 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 750 mg BID HBr will be administered daily

Intervention Type: DRUG

Rociletinib

Phase 1: Rociletinib 1000 mg BID HBr will be administered in escalating dosages in a period of 21-day cycles

Phase 2: Rociletinib 1000 mg BID HBr will be administered daily

Intervention Type: DRUG

Other Intervention Names

CO-1686; CO-1686; CO-1686; CO-1686; CO-1686; CO-1686

Eligibility Criteria

Inclusion Criteria

1. Metastatic or unresectable locally advanced NSCLC

2. Evidence of a tumor with one or more EGFR mutations excluding exon 20 insertion

3. Biopsy of either primary or metastatic tumor tissue within 60 days of dosing

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

5. Minimum age of 18 years

6. Adequate hematological and biological function

7. 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

Exclusion Criteria

Any of the following criteria will exclude patients from study participation:

1. Documented evidence of an Exon 20 insertion activating mutation in the EGFR gene

2. Active second malignancy

3. Known pre-existing interstitial lung disease

4. 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).

5. Treatment with prohibited medications less than or equal to 14 days prior to treatment with rociletinib

6. 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

7. Prior treatment with rociletinib or other drugs that target T790M positive mutant EGFR with sparing of wild type EGFR

8. Certain cardiac abnormalities or history

9. Non-study related surgical procedures less than or equal to 7 days prior to administration of rociletinib

10. Females who are pregnant or breastfeeding

11. Refusal to use adequate contraception for fertile patients (females and males) for 12 weeks after the last dose of rociletinib

12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study

13. Any other reason the investigator considers the patient should not participate in the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope National Medical Center

Duarte, California, United States

Compassionate Care Research Group, Inc.

Fountain Valley, California, United States

University of Southern California, Norris Comprehensive Cancer Center

Los Angeles, California, United States

Samuel Oschin Cancer Center

Los Angeles, California, United States

University of California, Irvine

Orange, California, United States

University of California Davis Medical Center

Sacramento, California, United States

UCLA Health System

Santa Monica, California, United States

Stanford Cancer Institute

Stanford, California, United States

East Valley Hematology and Oncology Medical Group, Inc.

Whittier, California, United States

The Oncology Institute of Hope and Innovations

Whittier, California, United States

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Georgetown University Hospital

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

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, United States

Florida Hospital Cancer Institute

Orlando, Florida, United States

University Cancer & Blood Center

Athens, Georgia, United States

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

Chicago, Illinois, United States

University of Maryland

Baltimore, Maryland, United States

Mass General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Karmanos Cancer Care Institute

Detroit, Michigan, United States

Regional Cancer Care Associates

Morristown, New Jersey, United States

Regional Cancer Center

New Brunswick, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Monter Cancer Center

Lake Success, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Ohio State University, Comprehensive Cancer Center

Columbus, Ohio, United States

Tulsa Cancer Institute

Tulsa, Oklahoma, United States

Providence CancerCenter Oncology and Hematology Care Clinic-Eastside Portland

Portland, Oregon, United States

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

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

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Swedish Cancer Institute

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Peter MacCallum Cancer Centre

East Melbourne, , Australia

Centre Hospitalier Universitaire de Grenoble

Grenoble, Auvergne-Rhône-Alpes, France

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Centre Antoine Lacassagne

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

Centre François Baclesse

Caen, , France

Centre Hospitalier Intercommunal Créteil

Créteil, , France

Centre Hospitalier Régional Universitaire de Lille

Lille, , France

Institut Gustave Roussy

Villejuif, , France

Med University Gdansk

Gdansk, , Poland

Countries

United States; Australia; France; Poland

References

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.

Reference Type: DERIVED

PMID: 29216356 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25923550 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

CO-1686-008

Identifier Type: -

Identifier Source: org_study_id