Patient case: 56-year-old female with basal cell carcinoma; genetic feature: PTCH1

Clinical trial: Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid Cancer

Summary: Medullary thyroid cancer (MTC) is an uncommon thyroid malignancy comprising of up to 5% of all thyroid cancers. The National Cancer Institute (NCI) estimates that 56,460 Americans will be diagnosed with thyroid cancer and 1,780 will die from the disease in 2012. Early disease is usually only confined to the thyroid and can be cured with surgery. Unfortunately, more than 50% of cases are diagnosed with locally advanced or metastatic disease, and a 10-year survival for them is about 40%. In most tumors, as well as in MTC, single-agent inhibitor therapy has faced numerous problems and has often provided patients with only limited benefits. In this study, the investigators will be using the results of a previous study in which the Drosophila animal model combined with extensive pretesting genetic analysis of samples taken from patients' individual tumors was used to potentially develop personalized therapeutic plans for those enrolled. In this study, the investigators will offer to treat those patients with their personalized therapeutic plan (if they were able to develop one in the prior study).
  This is a therapeutic clinical trial in which the investigators will provide personalized therapy to patients with medullary thyroid cancer based on a Personalized Therapeutic Plan (PTP) developed under the separate Tumor Genomic Analysis and Molecular Testing for Personalized Cancer Therapy protocol (GCO# 14-0054 (0001) MSSM). This therapeutic protocol applies only to the treatment period of Personalized Medicine. The objective is to establish superiority of Personalized Medicine in terms of efficacy (Overall Response Rate) in MTC patients, or substantially similar efficacy but with reduced toxicity, when compared to the best standard of care option for recurrent/metastatic MTC (currently cabozantinib) as was demonstrated in a phase III trial.

Detailed description: Patients will be offered the option to consent for enrollment to receive care based on the personalized treatment plan developed under the separate Tumor Genomic Analysis and Molecular Testing for Personalized Caner Therapy protocol. Each patient enrolled in this therapeutic study will be consented using an individualized consent form which addresses their respective personalized treatment plan and its associated risks. No genetic sequencing, and no testing involving flies or animals will be conducted under this therapeutic protocol. This protocol applies only to the treatment phase of personalized medicine. Study participation is expected to last 2-3 years.
  Personalized Treatment Plan Since each personalized treatment plan may, and probably will be, different from respected registration label and from FDA indication, a body of experts established as the Pharmacology Committee will review the ADMET data for the drugs from each of the selected regimens. For each case, a referring medical oncologist will provide a clinical presentation of the patient`s history of cancer and previous therapy, as well as other important medical history to a Multidisciplinary Tumor Board of Experts (MTBE) consisting of two pharmacologist scientists selected for experience in drug selection, a research clinical pharmacist, 2 medical oncologists with expertise with phase 2 clinical trials, a member of the IRB, two medical oncologists with expertise in the patient's tumor type including the treating physician and two scientists who performed the drug prediction tests. Except for clinicians and other investigators directly involved with the patient's care, the members of the MTBE will be an independent group as to avoid the risk of bias. The composition of this committee will vary and other individuals may be added as the process moves forward.
  A study subject will only be allowed to start the personalized therapeutic plan once the final informed consent is approved by the IRB and signed by the study subject. Once enrolled in a personalized therapy, the study subject will receive treatment based on the PTP and any dose adjustment will be according with the manufacturer label information and/or the PDR Electronic Library. Any controversial, incidental, or unexpected findings while on the treatment will be presented to the MTBE-called ad hoc, and the board will decide on continuation, dose adjustment or any modification of the study subject`s personalized therapeutic treatment plan.
  The Personalized Treatment Plan (PTP) will be stopped upon disease progression. However, if there is no standard therapy or no other clinical trial available at the time of progression, subjects with progressive disease will have the option of being treated with one of the graded therapies discussed at the initial MTBE meeting (there will be up to 5 therapeutic plans. They will be required to sign a separate informed consent but will not be included in statistical analysis of this protocol. All the statistics will be descriptive in nature and will be exploratory.

Eligibility: Inclusion Criteria:
  -  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 for use in this therapeutic clinical trial
  -  Histologically confirmed MTC by a Mount Sinai pathologist
  -  Recurrent/metastatic or incurable MTC
  -  Age > 18 years old
  -  Life expectancy must exceed 1 year from enrollment in the study
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
  -  The subject has documented worsening of disease (progressive disease) at screening compared with a previous CT scan or MRI image done within 14 months of screening Documentation of progression may be made by CT, MRI, or PET assessment
  -  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 enrolment
  Exclusion Criteria:
  -  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 CHF (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 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 antihypertensive 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

Relevance to patient case: not relevant