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Study to Assess the Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on Genomic Alterations

NCT02795156

Description:

With the increased availability of next-generation sequencing, oncologists are starting to incorporate genomic profiling into routine care of cancer patients. If a genomic alteration is identified during profiling, it could help guide the choice of therapy and improve treatment outcomes. This study will examine the anti-tumor activity of selected commercially available molecularly matched targeted therapies in patients who have failed first-line treatment for one of the following tumor types: non-small cell lung cancers; urothelial cancer; non-colon gastrointestinal cancers, and upper aerodigestive tract cancer.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Gastrointestinal Stromal Tumor
  • Hepatobiliary Neoplasm
  • Lip and Oral Cavity Carcinoma
  • Malignant Laryngeal Neoplasm
  • Malignant Salivary Gland Neoplasm
  • Nasal Cavity and Paranasal Sinus Carcinoma
  • Nasopharyngeal Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Oropharyngeal Carcinoma
  • Pancreatic Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study to Assess the Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on <span class="go-doc-concept go-doc-keyword">Genomic</span> Alterations

Title

  • Brief Title: Study to Assess the Activity of Molecularly Matched Targeted Therapies in Select Tumor Types Based on Genomic Alterations
  • Official Title: Phase II Study to Evaluate the Activity of Commercially Available Molecularly Matched Targeted Therapies in Selected Tumor Types Based on Genomic Alterations
  • Clinical Trial IDs

    NCT ID: NCT02795156

    ORG ID: SCRI PRO 10

    Trial Conditions

    Non-small Cell Lung Carcinoma

    Urothelial Carcinoma

    Gastrointestinal Carcinoma, Non-colon

    Upper Aerodigestive Tract Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    afatinib Gilotrif afatinib
    regorafenib Stivarga regorafenib

    Trial Purpose

    With the increased availability of next-generation sequencing, oncologists are starting to
    incorporate genomic profiling into routine care of cancer patients. If a genomic alteration
    is identified during profiling, it could help guide the choice of therapy and improve
    treatment outcomes. This study will examine the anti-tumor activity of two FDA-approved
    therapies to treat patients who were previously profiled with next-generation sequencing
    technology and who failed first-line treatment for one of the following tumor types:
    non-small cell lung cancers; urothelial cancer; non-colon gastrointestinal cancers, and
    upper aerodigestive tract cancer.

    Detailed Description

    This pilot study will evaluate preliminary antitumor activity of two FDA-approved targeted
    therapies, regorafenib (Stivarga, Bayer) and afatinib (Gilotrif, Boehringer Ingelheim) in
    patients who have either failed first-line treatment, or for which no standard treatment is
    available, for one of the following four tumor types:

    1. non-small cell lung cancer,

    2. urothelial carcinoma,

    3. non-colon gastrointestinal cancers, and

    4. upper aerodigestive tract cancers (lip, tongue, salivary glands, gum, mouth, oral
    cavity, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and larynx tumors).

    Approximately 160 patients (40 per tumour type) are planned for enrollment. Consideration
    for enrollment will be based on results from profiling with next-generation sequencing
    technology that was performed outside of the protocol. Eligible patients will receive one of
    the FDA-approved targeted agents at the recommended dose. The treating physician will decide
    which targeted agent to prescribe based on the genomic alterations per tumor type and the
    targets listed in the package insert for each agent.

    Trial Arms

    Name Type Description Interventions
    regorafenib Experimental Patients with genomic alterations in the following genes, as determined by next-generation sequencing, will be assigned at the investigator's discretion to treatment with regorafenib: RET, VEGF1-3, KIT, PDGFR- and -, FGFR1-2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, SAPK2, PTK5, Ab1. regorafenib
    afatinib Experimental Patients with genomic alterations in the following genes, as determined by next-generation sequencing, will be assigned at the investigator's discretion to treatment with afatinib: EGFR, HER2, HER4. afatinib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with a histologically or cytologically confirmed diagnosis of one of the
    following tumor types whose disease has progressed following one line of standard
    therapy and/or for which no standard treatment is available that has been shown to
    prolong survival:

    1. Non-small cell lung cancer

    2. Urothelial carcinoma

    3. Non-colon gastrointestinal cancers (including hepatobiliary, pancreatic, and
    gastroesophageal tumors)

    4. Upper aerodigestive tract cancers (including lip, tongue, salivary gland, gum,
    oral cavity, mouth, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and
    larynx tumors)

    - Patients must have a predefined genomic alteration that can be targeted with either
    afatinib or regorafenib

    - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

    - Adequate hematologic, hepatic and liver function.

    - Patients who are therapeutically treated with an agent such as warfarin or heparin
    are allowed provided their dose and INR/PTT are stable. Close monitoring is
    mandatory.

    - Must comply with instructions to prevent contraception.

    - Must be willing and able to comply with study and follow-up procedures.

    - Must be able to understand the nature of the study and give written informed consent.

    Exclusion Criteria:

    - Two or more prior chemotherapy regimens in the metastatic setting.

    - Most recent chemotherapy 3 weeks and > Grade 1 chemotherapy-related side effects,
    with the exception of neuropathy (> grade 2 excluded) and alopecia.

    - Use of a study drug or targeted therapy 21 days or 5 half-lives (whichever is
    shorter) prior to the first dose of study treatment. For study drugs for which 5
    half-lives is 21 days, a minimum of 10 days between termination of the study drug
    and administration of study treatment is required.

    - Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
    administered 28 days or limited field radiation for palliation 7 days prior to
    starting study drug or has not recovered from side effects of such therapy.

    - Major surgical procedures 28 days of beginning study drug, or minor surgical
    procedures 7 days. No waiting required following port-a-cath placement.

    - Previously untreated brain metastases. Patients who have received radiation or
    surgery for brain metastases are eligible if therapy was completed at least 2 weeks
    prior to study entry and there is no evidence of central nervous system disease
    progression, mild neurologic symptoms, and no requirement for chronic corticosteroid
    therapy. Enzyme-inducing anti-convulsants are contraindicated.

    - Pregnant or lactating

    - Acute or chronic liver, renal, or pancreas disease.

    - Presence of active gastrointestinal disease or other condition that will interfere
    significantly with the absorption, distribution, metabolism, or excretion of oral
    therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade 2,
    and malabsorption syndrome).

    - Any of the following cardiac diseases currently or within the last 6 months:

    - Unstable angina pectoris

    - Congestive heart failure (New York Heart Association (NYHA) Grade 2)

    - Acute myocardial infarction

    - Conduction abnormality not controlled with pacemaker or medication

    - Significant ventricular or supraventricular arrhythmias (patients with chronic
    rate-controlled atrial fibrillation in the absence of other cardiac
    abnormalities are eligible)

    - Valvular disease with significant compromise in cardiac function

    - Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg
    or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels
    must have their blood pressure (BP) controlled with medication prior to starting
    treatment).

    - Thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident
    (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism
    within 6 months of start of treatment.

    - Evidence or history of bleeding diathesis or coagulopathy; any haemorrhage or
    bleeding event NCI CTCAE Grade 3 within 4 weeks prior to start of treatment.

    - Presence of a non-healing wound, non-healing ulcer, or bone fracture.

    - Patients with phaeochromocytoma.

    - Serious active infection at the time of treatment, or another serious underlying
    medical condition that would impair the ability of the patient to receive protocol
    treatment.

    - Known diagnosis of human immunodeficiency virus, hepatitis B or C.

    - Presence of other active cancers unless indolent and not requiring therapy. Patients
    with Stage I cancer who have received definitive local treatment and are considered
    unlikely to recur are eligible. All patients with previously treated in situ
    carcinoma (i.e., non-invasive) are eligible, as are patients with history of
    non-melanoma skin cancer.

    - Psychological, familial, sociological, or geographical conditions that do not permit
    compliance with the protocol.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall response rate (ORR)

    Secondary Outcome Measures

    Clinical benefit rate

    Time to treatment failure

    Progression-free survival

    Trial Keywords

    regorafenib

    afatinib

    targeted therapy