A Study of Entrectinib (RXDX-101) for the Treatment of Patients with Solid Tumors that have NTRK1/2/3, ROS1, or ALK Gene Rearrangements

Overview

About this study

The purpose of this study is to determine the response of entrectinib (RXDX-101) for the treatment of patients with solid tumors that have an NTRK1/2/3, ROS1, or ALK gene rearrangement.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

Inclusion Criteria:

  • Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement
    • Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria. 
    • US Only: Other hematological malignancies (e.g., acute leukemia, myeloma, etc.) are also known to potentially harbor a gene rearrangement of interest. Although these patients are not eligible for study enrollment, they may be eligible for treatment under a Single Patient Protocol. Please make all such requests directly to the Sponsor.
  • For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Foundation Medicine, Inc. or to the alternative, approved central laboratory for that region.
  • Measurable disease as assessed locally using RECIST v1.1.
  • Note: Patients with non-measurable disease (evaluable disease only) will be eligible for enrollment in the “non-evaluable for the primary endpoint” basket and will mainly contribute to assessment of safety, PK, and other secondary endpoints.
  • Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed. The use of seizure prophylaxis is allowed as long as patients are taking non-enzymeinducing anti-epileptic drugs (non-EIAEDs). If patients were previously on EIAEDs and these have been discontinued, they must have been discontinued for at least 2 weeks prior to the start of entrectinib treatment. If patients require an anti-epileptic medication, a CYP3A4 non-EIAED can be used such as levetiracetam, valproic acid, gabapentin, topiramate, or lacosamide. Patients requiring steroids must be at stable or decreasing doses for at least 2 weeks prior to the start of entrectinib treatment.
  • Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK (non-NSCLC patients only) inhibitors in patients who have tumors that harbor those respective gene  rearrangements).
    • Note: The ALK basket is closed to enrollment.
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy, respectively, at the time of the start of entrectinib treatment.
    • Note: For targeted therapies, there must be no signs of disease flare or accelerated disease progression after treatment discontinuation.
  • At least 4 weeks must have elapsed since completion of antibody-directed therapy at the time of the start of entrectinib treatment.
  • Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment. Patients who received brain irradiation must have completed whole brain radiotherapy at least 14 days prior and/or stereotactic radiosurgery at least 7 days prior to the start of entrectinib treatment.
  • Age ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life expectancy of at least 4 weeks.
  • Adequate liver function as defined by the following criteria:
    • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤ 3.0 × upper limit of normal (ULN); ≤5.0 × ULN if liver metastases are present;
    • Total serum bilirubin ≤ 2.0 × ULN; patients with a known history of Gilbert’s syndrome and/or isolated elevations of indirect bilirubin are eligible.
  •  Females of childbearing potential must have a negative serum pregnancy test during Screening and must not be breastfeeding or intending to become pregnant during the study. Female patients will be considered to be of childbearing potential unless they have undergone permanent contraception or are postmenopausal. Postmenopausal is defined as at least 12 months without menses with no other medical reasons (e.g., chemical menopause due to anticancer treatment).
  • Ability to swallow entrectinib intact without chewing, crushing, or opening the capsules.
  • Willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to the start of entrectinib treatment.

Exclusion Criteria:

  • Current participation in another therapeutic clinical trial.
  • Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements.
    • Note: In cases where the patient was intolerant to prior Trk, ROS1, or ALK inhibitors, please discuss with the Sponsor.
  • In addition, prior treatment with crizotinib is permitted ONLY in ALK- or ROS1-rearranged NSCLC patients presenting with radiographically-confirmed CNS only progression. Other ALK or ROS1 inhibitors are prohibited in that scenario.
    • Note: The ALK-rearranged NSCLC basket for patients previously treated with crizotinib and presenting with CNS-only progression is closed for further enrollment.
  • History of other previous cancer that would interfere with the determination of safety or efficacy of entrectinib with respect to the qualifying solid tumor malignancy.
    • Note: Patients presenting with dual primary cancers may enroll in the “nonevaluable for the primary endpoint” basket if at least one of the cancers harbor an NTRK1/2/3, ROS1, or ALK gene rearrangement as per Inclusion Criterion 1.
  • Incomplete recovery from any surgery prior to the start of entrectinib treatment that would interfere with the determination of safety or efficacy of entrectinib.
  • Any condition (in the past 3 months) that would interfere with the determination of safety or efficacy of entrectinib: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, stroke, symptomatic bradycardia, or uncontrolled arrhythmias requiring medication.
  • History of recent (within the past 3 months) symptomatic congestive heart failure or ejection fraction ≤ 50% observed during screening for the study.
  • History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds from ECGs performed at least 24 hours apart).
  • History of additional risk factors for torsades de pointes (e.g., family history of long QT syndrome).
  • Peripheral sensory neuropathy Grade ≥ 2.
  • Known active infections that would interfere with the assessment of safety or efficacy of entrectinib (bacterial, fungal, or viral, including human immunodeficiency virus positive).
  • Active gastrointestinal disease (e.g., Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
  • Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis.
    • Note: Radiation-induced lung disorders are not included in this exclusion criterion.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Helen Ross, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Helen Ross, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Helen Ross, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions