Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity

Inclusion Criteria: 1. Males and Females; Ages 6-28 years (inclusive) 2. History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist (for example, change in BMI z-score \> 0.2 and/or BMI +5% during the first 6 months following tumor treatment) 3. Obesity (BMI \> 95th%ile for age/sex using CDC 2000 reference for under 18; BMI \> 30 kg/m2 for 18+ years) 4. Recent evidence of hypothalamic injury by brain MRI with central review; \>6 months status-post definitive therapy (surgery, chemotherapy, or radiation); no major operations/surgeries planned during the study period. 5. Stable on pituitary replacement\* and/or appetite-modulating medications (including stimulants) for at least 2 months. \*Adjustments of less than 25% (\<25%) are permitted to hydrocortisone, growth hormone or thyroid hormone. Sex steroids and DDAVP are exempt. 6. Post-menarchal females must use a highly effective form of contraception, unless hypogonadotropic hypogonadism is documented. All participating females of child-bearing potential will have pregnancy testing as outlined in the protocol. 7. Participants must be able to communicate well with the investigative team, must comply with requirements of the study, and be able to provide written informed consent and/or assent for individuals less than 18y with consent of a parent/legal guardian. Exclusion Criteria: 1. Contraindication to Phentermine, Topiramate, or Qsymia as assessed using current package inserts. Including: History of glaucoma and known hyperthyroidism. 2. Known history of nephrolithiasis (kidney stones). 3. Current clinical diagnosis of anorexia nervosa or bulimia nervosa in the medical record. 4. Known history of metabolic acidosis, low bicarbonate on screening laboratory assessment (below lower limit of normal), or clinically significant bone disease requiring medication (beyond calcium and/or vitamin D). 5. Current or recent (\<14 days) use of monoamine oxidase inhibitor. 6. Known hypersensitivity to sympathomimetic amines. 7. Clinically significant cardiovascular conditions, as defined as any of the following: i) abnormal blood pressure, defined as: under 13y, 95th%ile +12 mm Hg or \> 140/90, whichever is lower; 13y and older, \> 140/90 ; ii) history of cardiac arrhythmia or arrhythmia detected on screening ECG; iii) history of heart failure and/or cardiomyopathy; iv) prolonged QTc interval (QTc \> 460 msec), and/or long QT syndrome phenotype and/or positive genotype for long QT syndrome pathogenic; v) history of cardiac disease including coronary artery disease. 8. Females who are pregnant, breastfeeding, or planning to become pregnant during the trial. 9. "Brittle" diabetes insipidus (in the opinion of the referring endocrinologist, e.g. requiring frequent hospitalizations and/or frequent abnormal sodium values). 10. Diabetes mellitus requiring insulin/secretagogue. HbA1c \> 8.5% at Screening. 11. Clinically significant hyperthyroidism as assessed using thyroid hormone measurements. Clinical measurements within 12 months of baseline/screening may be used to assess this criterion. 12. History of clinically significant hypokalemia (low potassium) or current clinically significant hypokalemia (low potassium) on baseline/screening labs. 13. Clinically significant liver disease and/or known severe hepatic impairment. ALT \> 3 x Upper Limit of Normal (ULN) AST \> 3 x ULN 14. Clinically significant kidney disease. GFR\<60 ml/min/1.73m2 15. History of seizure in the 12 months prior to Screening. 16. History of substance abuse, depression of moderate or greater severity, psychiatric disorder and/or suicidality. 17. History of abdominal surgery including gastric bypass. 18. Current use of supra-physiologic steroids. 19. History of allergy or sensitivity to test agents. Including individuals with known aspirin allergy or hypersensitivity and/or known allergy to FD\&C Yellow No. 5 (tartrazine). 20. Concurrent use of carbonic anhydrase inhibitors. 21. Concurrent use of non-potassium sparing diuretics. 22. New weight management medication (or \>5% decrease in weight over prior 2 months on any current, stable regimen), stimulant, and/or investigational medication within 2 months prior to screening, and/or plans to initiate other new weight management regimen. 23. Cognitive impairment that, in the opinion of the investigator, precludes participation in the study. 24. Individuals considered, in the Investigator's opinion, not suitable to participate in the study for reasons other than those indicated above.