Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA

Summary: It was found that people who have an excessive growth in one or more parts of their body and normal growth in other parts, may have a change in genes responsible for controlling cell growth. This genetic discovery identified a possible treatment for this overgrowth, called Sirolimus.
  This is a pilot study, which help the investigators prepare a larger international study, which will aim to determine whether a treatment based Sirolimus is able to stop the excessive growth of one or more parties of their body in people who carry a genetic change in the PIK3CA gene (phosphatidylinosilol-3-kinase encoded by the gene PIK3CA).

Detailed description: The duration of participation is 15 months:
  -  Visit screening: blood test, pre-clinical evaluation, urine collection and chest X-ray.
  -  First 6 months: participants will have their overgrowth monitored. This step includes 2 visits taking place at the University Hospital of Dijon: complete clinical evaluation, MRI of the body part by the overgrowth and Dual-energy X-ray absorptiometry (DXA).
  -  Next 6 months: participants will take Sirolimus. This step includes 2 visits (4 and 13 weeks after the start of treatment at local hospital): blood test, urine collection and clinical evaluation.
  and 1 end of study visit after 6 months of treatment taking place at the University Hospital of Dijon: blood test, complete clinical evaluation, urine collection, MRI and DXA.
  Participants will have several blood and urine tests between visits (1 and 2 weeks after the start of treatment at a local laboratory).

Eligibility: Inclusion Criteria:
  -  Post-zygotic PIK3CA mutation
  -  Age: 3-65 years
  -  Measurable overgrowth, in current progression or with clinical history of overgrowth progression
  -  Patient clinically stable
  -  Presence of a disability, social or cosmetic impairment requiring treatment from the patient perspective,
  -  Written informed consent form signed and dated by the subject or by the patient's legal representative
  Exclusion Criteria:
  -  Pregnancy or lactation
  -  Women and men of reproductive age without any effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
  -  Hypersensitivity to the active substance (sirolimus) or to any of the excipients
  -  Impossibility to obtain written informed consent form signed by the subject or the patient's legal representative, or vulnerable adults
  -  Treatment with Sirolimus in the last 4 weeks before the trial
  -  Personal history of malignancy or current investigations for suspected malignancy
  -  Active skin infection requiring antibiotics or antiviral treatments
  -  HIV or hepatitis B or C infection
  -  Past history of Mycobacterium tuberculosis infection
  -  Active pneumopathy
  -  Uncontrolled infection
  -  Chronic liver disease (ASAT or Alanine amino transférase (ALAT)> 3 times upper normal limit)
  -  Stage 3 (or more) chronic renal insufficiency (eGFR< 60mls/min)
  -  Neutropenia with neutrophiles < 1.0 x10^9/L
  -  Uncontrolled dyslipidemia
  -  Inability to attend study visits

Relevance to patient case: not relevant