Trametinib in Treating Patients with Solid Tumors, Metastatic Medullary Thyroid Cancer or Colorectal Cancer
- Patients already enrolled to the separate Tumor Genomic Analysis and Molecular Testing for Personalized Cancer Therapy study, for which a personalized therapeutic plan has been successfully created under that protocol and selected by the multidisciplinary tumor board of experts (MTBE) for use in this therapeutic clinical trial
- Histologically confirmed cancer by a Mount Sinai pathologist
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
- Patients with a recurrent/metastatic or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists or is too toxic
- The subject has documented worsening of disease (progressive disease) at screening compared with a previous computed tomography (CT) scan or magnetic resonance imaging (MRI) image done within 14 months of screening documentation of progression may be made by radiological (CT, MRI, or positron emission tomography [PET]), clinical or serological assessment; if documentation is radiological, screening scan be compared to any previous scan (CT, MRI or PET) within 14 months of cycle 1 day 1 (C1D1)
- Adequate organ and bone marrow function defined by routine testing
- The subject has no other diagnosis of cancer (unless non-melanoma skin cancer, an early form of cervical cancer, or another cancer diagnosed >= 2 years previously) and currently has no evidence of active other malignancy (unless non-melanoma skin cancer or an early form of cervical cancer)
- Signed and dated informed consent form indicating that the patient has been informed of all pertinent aspects of the trial prior to enrollment
- Patients who are currently receiving and responding to a different course of anti-neoplastic therapy, within the limits of acceptable toxicity per standard clinical practice, may not be enrolled to this study
- Current symptomatic brain metastases; if previously present, the metastases must have been treated at least two months before participation in this study; CT or MRI scan of the brain is mandatory to assess the presence or not of brain metastases
- History of other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or basal cell, or squamous cell carcinoma of the skin
- History of significant cardiac disease defined as: * Symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] classes III-IV) * High-risk uncontrolled arrhythmias; i.e. atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia or higher-grade atrioventricular (AV) block (second degree AV-block type 2 [mobitz 2] or third degree AV-block) * Prolongation of QT interval > 480 msecs * History of myocardial infarction within last 12 months * Clinically significant valvular heart disease * Angina pectoris requiring anti-angina treatment * Current uncontrolled hypertension (persistent systolic > 180 mmHg and/or diastolic > 100 mmHg); initiation or adjustment of anti-hypertensive medication is permitted prior to study entry
- Evidence of active bleeding or bleeding diathesis
- Cerebrovascular accident at any time in the past, transient ischemic attack, deep venous thrombosis or pulmonary embolism in the past 6 months
- Current severe, uncontrolled systemic disease
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Failure to use contraception in patients with preserved reproductive capacity
- Any other medical condition for which the treating physicians deem might lead to unacceptable toxicity or morbidity for that treatment plan for the patient e.g., allergy to a component of therapy or a medical condition that might be aggravated by the therapy and increases potential risk of toxicity in the opinion of the treating physicians
I. To compare efficacy of treatment given under Personalized Therapeutic Treatment Plans (PTTPs), as developed under the separate Tumor Genomic Analysis for Personalized Cancer Therapeutics protocol, to the best arm of a Phase III trial in this disease category – for example cabozantinib for medullary thyroid cancer (MTC) using objective response rate (ORR) defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, or regorafenib for colorectal cancer (CRC) using the proportion of subjects who remained progression-free at 3 months using RECIST 1.1 criteria.
II. To compare efficacy of treatment given under personalized treatment plans (PTPs) to the best arm of a phase III trial in this disease category for progression free survival (PFS).
III. To compare efficacy of treatment given under PTPs to the best arm of a phase III trial in this disease category for toxicity.
IV. To establish a preliminary efficacy signal and/or identification of subsets of patients most likely to benefit from the personalized medicine given under personalized therapeutic plans (PTTPs), as developed under the separate Tumor Genomic Analysis for Personalized Cancer Therapeutics protocol.
I. To correlate specific (normal or various primary and secondary genetic abnormalities) with clinical and laboratory parameters.
II. To correlate specific karyotype groups with response rates, response duration, survival and cure in patients treated with various treatment regimens.
III. To correlate specific karyotype groups with multi-drug resistance data.
IV. To correlate specific karyotype groups with epidemiologic data (toxic exposure) and family history.
V. To identify new genetic abnormalities important in tumorigenesis.
Patients receive trametinib orally (PO) once daily (QD) on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days and then every 4-6 months.
Trial Phase Phase II
Trial Type Treatment
Icahn School of Medicine at Mount Sinai
Krzysztof J. Misiukiewicz
- Primary ID 15-0146
- Secondary IDs NCI-2017-01026
- Clinicaltrials.gov ID NCT02363647