None listed
Conditions
Brief summary
LU-TEMP is a single-site pilot clinical trial of combination therapy with lutate and temozolomide for participants who have inherited from their parents a gene change called succinate dehydrogenase (SDH) and who have a tumor called pheochromocytoma or paraganglioma. The trial asks the question of whether combination therapy with lutate and temozolomide can reduce disease progression and improve survival. Who is it for? You may be eligible to be involved in this trial if you have pheochromocytoma or paraganglioma associated with a gene change called succinate dehydrogenase and are 18 years or older. Study details Participants will be enrolled in the study, attend standard of care treatment and follow up visits at 3 months after the completion of treatment. The intervention is an intravenous infusion once every 6 weeks and an oral capsule on days 10-14 of every 6 week cycle. Participants are asked to complete additional quality of life surveys. The total duration of follow up is 24 months as participants will receive a brief phone call at 24 months. The data will be used to improve treatment of participants living with pheochromocytoma or paraganglioma. It is anticipated that if the objectives of this pilot study are met successfully, a larger Phase 2 study will follow.
Interventions
This is pilot clinical trial of intravenous lutate administered with oral temozolomide, repeated up to 4 cycles in participants with succinate dehydrogenase (SDH)-associated locally advanced or metastatic pheochromocytoma and paraganglioma (PPGL).
Intravenous lutate 7.5-8 GBq will be administered on Day 1 of each cycle. The duration of each cycle is6 to 10-weeks. Temozolomide will be administered to participants as oral capsules at an initial dose of 150mg/m2/day on Days 10-14 of a 6 to 10-wee
This is pilot clinical trial of intravenous lutate administered with oral temozolomide, repeated up to 4 cycles in participants with succinate dehydrogenase (SDH)-associated locally advanced or metastatic pheochromocytoma and paraganglioma (PPGL). Intravenous lutate 7.5-8 GBq will be administered on Day 1 of each cycle. The duration of each cycle is6 to 10-weeks. Temozolomide will be administered to participants as oral capsules at an initial dose of 150mg/m2/day on Days 10-14 of a 6 to 10-week cycle and in patients with a good tolerance during the first cycle the dose will increase to 200mg/m2/day on Days 10-14 of a 6 to 10-week cycle. For temozolomide the frequency of administration will be once daily or twice daily depending on the calculated total daily dose, according to Cancer Institute NSW guidelines. Dose modification will occur according to standard practice. The total treatment regimen takes approximately 32 weeks. The total number of cycles and duration of each cycle will be determined by toxicity. If there is no toxicity, the participants will receive 4 cycles for duration 6 weeks. If there is toxicity, treatment may be dose reduced and delayed for up to a 10 week interval between cycles. Participants with poor tolerance to temozolomide will not remain on the same initial dose, they will receive a decreased dose. If toxicity is severe or ongoing the patient may receive less than 4 cycles. The total number of cycles and duration of each cycle as determined by toxicity is in keeping with standard practice guidelines (Cancer Institute NSW Guidelines on Neuroendocrine Tumours Advanced 2018, TGA Product and Consumer Medicine Information for Temozolomide and Lutathera Product and Consumer Information). Study drug accountability records will record the date, quantity of used and unused study drug returned. The patient will return unused study drug and packaging. The investigator will count to ensure the patient took the correct dose, ask the patient to confirm they took all the missing drugs and did not throw it out any study drug.
Sponsors
Royal North Shore Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent 2. PPGL diagnosed histopathologically (after biopsy or tumor resection) or high suspicion on imaging and biochemistry 3. SDH mutation confirmed on genetic testing 4. Patient age 18 years or older. 5. Locally advanced (defined as local invasion to surrounding structures) or metastatic (defined as occurrence of a tumour at a site where neural crest cells are not usually found, such as in bones, lungs, and liver) PPGL 6. Somatostatin receptor (SSTR) uptake on a 68Ga- DOTATATE positron emission tomography (DOTATATE PET) scan higher than the background liver activity, defined as Krenning score 3 or 4
Exclusion criteria
1. Impaired haematological function defined by the following laboratory values: • Anaemia (Hb < 90 g/L) • White blood cell count < 2 x 10^9 / L • Neutropenia (neutrophil count < 1.5 x 10^9 / L) • Thrombocytopenia (platelet count < 100 x 10^9/L) 2. Impaired kidney function defined by the following laboratory value: • Glomerular filtration rate (GFR) < 40 ml/min/1.73m^2 3. Impaired hepatic function defined by the following laboratory values: • Total serum bilirubin greater than or equal to 75 micromoles/L or greater than or equal to 1.5 x upper limit normal (unless Gilbert’s syndrome) • Albuminemia < 25 g/L • Prothrombin ratio decreased < 70% 4. Active hepatitis B infection 5. Previous external beam radiotherapy involving more than 25% of the bone marrow 6. Severe uncontrolled heart failure defined as class III or IV in the New York Heart Association (NYHA) classification 7. Pregnancy 8. Breastfeeding 9. Unwilling to use reliable contraception or avoid pregnancy or avoid sperm donation during treatment and for a minimum of the following 6 months after the end of the treatment 10. Receiving an investigational medicinal product within 30 days of screening
Outcome results
None listed