Please select the eligibility criteria that correspond to the clinical trial below.
Title: Placebo Controlled Double Blind Crossover Trial of Metformin for Brain Repair in Children with Cranial-Spinal Radiation for Medulloblastoma
Brief Summary: A placebo controlled double blind crossover trial of metformin in 30 children treated with radiation for medulloblastoma - the most common malignant brain tumour. The investigators used tests of thinking and learning and brain imaging techniques to examine whether metformin can enhance cognition or promote brain repair following radiation-induced brain injury.


Options:
A: Inclusion Criteria:

* Women
* Completed chemotherapy within past 2 years

  * completed for at least 3 months
* Self report cognitive dysfunction following chemotherapy
* Stage I-IIIA breast cancer
* Physically able to undertake moderate to vigorous physical activity program

Exclusion Criteria:

* Self report \> 90min/week of moderate physical activity (last 6 months)
* Mini-mental status exam score \< 23
* Co-morbid conditions that may alter cognitive testing results (i.e., a clinically diagnosed major depression, anxiety disorder, or other psychiatric condition, meeting DSM IV criteria)
* History of substance abuse
* Other neurological disorder (i.e., head injury, epilepsy, tumour, neurodegenerative disease)
* Ruled ineligible for MRI scanning (i.e., metal implants)
B: Inclusion Criteria:

1)age 18 and older at time of registration. 2) recursive partitioning class (RPA) I or II. 3) 1 to 3 newly diagnosed brain metastases 4) must be eligible to have all lesions treated by SRS as determined by the radiation oncologist on the basis of location and size. 5)MRI with contrast must be performed with 1 month of registration. 6)Signed informed consent form approved by the IRB agreeing to randomization .

Exclusion Criteria:

1) prior WBRT 2) prior resection of brain metastasis, SRS or Gamma knife. 3) \> 3 brain metastases present on MRI 4) lymphoma, small cell lung cancer, leukemia, germ cell tumors. 5) leptomeningeal disease. 6) unknown primary.7) RPA Class III (i.e. KPS \< 70) 8) pregnancy.

Post-entry exclusion: No post-entry exclusions will be allowed after registration has occurred. All randomized patients will be included in the analysis and those lost to follow-up will be assigned the least favorable outcome (recurrence, death).
C: Inclusion criteria: Survivors will be included if they:

1. Have been treated with cranial or cranial-spinal radiation,
2. Are between 5 and 21 years of age at time of consent, and
3. Either declare English as their native language or have had at least two years of schooling in English at the time of their baseline assessment.
4. Have been diagnosed with a brain tumour requiring treatment with cranial or cranial-spinal radiation at least 2 years ago, is not receiving active treatment and no more than 15 years may have elapsed between treatment with cranial-spinal radiation and time of the trial. Survivors with a shunt will be included in the trial, but will need to be identified prior to study enrollment to discuss any specific considerations for imaging.
5. Meet criteria for adequate organ function requirements:

   1. Adequate renal function defined as: Creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70ml/min/1.73 m2 or serum creatinine based on age/gender as follows:

      Maximum Serum Creatinine Level (mg/dL)

      5 to \< 10 years: Male = 1; Female = 1

      10 to \< 13 years: Male = 1.2; Female = 1.2

      13 to \< 16 years: Male = 1.5; Female = 1.4

      ≥ 16 years: Male = 1.7; Female = 1.4
   2. Adequate liver function defined as:

   Total bilirubin \< 1.5 x upper limit of normal (ULN) for age, and,

   serum glutamate oxaloacetate transaminase (SGOT) (AST) or serum glutamate pyruvate transaminase (SGPT) (ALT) \< 3 x upper limit of normal (ULN) for age.
6. Females of childbearing potential must have a negative pregnancy test result and must agree to use a medically acceptable method of contraception throughout the entire study period and for 30 days after the last dose of study drug.
7. Informed consent will be obtained from the participants and/or their legal guardians by study team members authorized to consent for this study.

Exclusion criteria: Survivors will be excluded if they

1. Are receiving palliative care.
2. Are unable to participate in neuro-imaging without sedation as this is the primary outcome measure for the trial.
3. Are unable to swallow tablets.
4. Are unstable and/or insulin-dependent (Type 1) diabetic patients.
5. Have acute or chronic metabolic acidosis and/or lactic acidosis.
6. Any female patient or partner who has reached menarche and male patients who are not willing to use an effective method of contraception.
7. Patient who is pregnant or lactating and does not agree to stop breastfeeding while receiving trial treatment.
8. Have a history of renal disease or renal dysfunction e.g., as suggested by elevated serum creatinine levels (see 5.a. Inclusion criteria) or abnormal creatinine clearance.
9. Have a history of congestive heart failure requiring pharmacologic treatment.
10. Have a known hypersensitivity to metformin hydrochloride.
D: Inclusion Criteria:

* The participant must be 18 years or older and Danish speaking.
* Performance status 0-2
* Capable of cooperating on testing
* Diagnosed with one of the following diagnoses according to WHO 2016 classification 16 and been treated between 2006 and 2016

  1. ZM93803 glioma (exclusive glioblastoma)
  2. ZM9401/3 anaplastic astrocytoma, IDH mutant
  3. ZM9400/3 diffuse astrocytoma, IDH-mutant
  4. ZM9411/3 gemistocytisk astrocytoma, IDH mutant
  5. ZM9400/3 diffuse astrocytoma, NOS
  6. ZM9451/3 anaplastic oligodendroglioma, IDH mutant and 1p/19q-co deleted
  7. ZM9450/3 oligodendroglioma, IDH mutant and 1p/19q-co deleted
  8. ZM9450/3 oligodendroglioma, NOS
  9. ZM9451/3 anaplastic oligodendroglioma, NOS
  10. ZM9530/0 meningioma
  11. ZM9470/3 medulloblastoma, NOS
  12. DD352A pituitary adenoma
  13. Other rare brain tumours including skull base sarcomas

      -

      Exclusion Criteria:

      Performance status 3-4 Progression after radiation therapy

      -

Answer: C