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Trial registered on ANZCTR


Registration number
ACTRN12621000802808
Ethics application status
Approved
Date submitted
21/04/2021
Date registered
25/06/2021
Date last updated
5/04/2023
Date data sharing statement initially provided
25/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot open label study of combination treatment lutate and temozolomide in the treatment of succinate dehydrogenase-associated pheochromocytoma and paraganglioma in adults.
Scientific title
A pilot open label study of [177Lu]Lu-octretotate and temozolomide in the treatment of succinate dehydrogenase-associated locally advanced or metastatic pheochromocytoma and paraganglioma in adults.
Secondary ID [1] 304011 0
Nil
Universal Trial Number (UTN)
U1111-1276-7523
Trial acronym
LU-TEMP
Linked study record
Nil

Health condition
Health condition(s) or problem(s) studied:
Cancer 321632 0
Condition category
Condition code
Cancer 319373 319373 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 320321 0
Treatment: Drugs
Comparator / control treatment
Historical controls from published literature. The source of historical data is from published literature of fifteen consecutive patients with malignant pheochromocytoma and paraganglioma over time period between November 2007 and September 2011 (Hadoux J, Favier J, Scoazec JY, Leboulleux S, Al Ghuzlan A, Caramella C, et al. SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. International journal of cancer. 2014;135(11):2711-20).
Control group
Historical

Outcomes
Primary outcome [1] 327229 0
Objective response rate (ORR) as assessed by radiological tumour response using RECIST criteria.

Data will be collected from the participant’s medical records, online hospital investigations programs and by the patient history and examination during study visits.
Timepoint [1] 327229 0
3 months following the last treatment session
Secondary outcome [1] 394304 0
Composite outcome: Disease progress as assessed by ORR by radiological tumour response using Krenning score, time to progression (TTP) by radiological tumour response using RECIST criteria, progression free survival (PFS) by radiological tumour response using RECIST criteria and radiological tumour response using the NETPET score.

Data will be collected from the participant’s medical records, online hospital investigations programs and by the patient history and examination during study visits.
Timepoint [1] 394304 0
3 months following the last treatment session
Secondary outcome [2] 394305 0
Survival as assessed by medical record review and survival phone calls (composite outcome).
Timepoint [2] 394305 0
3 months, 6 months, 12 months, 18 months and 24 months following the last treatment session.
Secondary outcome [3] 394307 0
Toxicities assessed by physical exam and patient reported symptoms (composite outcome).

Data will be collected from the participant’s medical records, online hospital investigations programs and by the patient history and examination during study visits.
Timepoint [3] 394307 0
3 months following the last treatment session
Secondary outcome [4] 394309 0
Health-related quality of life using EORTC QLQ-C30.

Data will be collected from patient completes questionnaire.
Timepoint [4] 394309 0
3 months following the last treatment session
Secondary outcome [5] 394310 0
Health-related quality of life using EQ-5D-5L.

Data will be collected from patient completes questionnaire.
Timepoint [5] 394310 0
3 months following the last treatment session

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size considerations for this study are not based on a power calculation. It is believed that the proposed sample size will allow a reliable assessment to be made based on the statistics that will be generated to support the study aims and endpoints. Final analysis will take place once all patients complete therapy and have attended the end of trial visit. Safety and efficacy data will be evaluated using descriptive statistics.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/06/2022
Actual
Date of last participant enrolment
Anticipated
21/03/2024
Actual
Date of last data collection
Anticipated
28/08/2026
Actual
Sample size
Target
4
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19163 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 33734 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 308391 0
Hospital
Name [1] 308391 0
Royal North Shore Hospital
Country [1] 308391 0
Australia
Primary sponsor type
Hospital
Name
Royal North Shore Hospital
Address
Royal North Shore Hospital Reserve Road St Leonards 2065 NSW
Country
Australia
Secondary sponsor category [1] 309221 0
None
Name [1] 309221 0
Address [1] 309221 0
Country [1] 309221 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308355 0
The Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 308355 0
Level 13 Kolling Building
Royal North Shore Hospital
Reserve Road
St Leonards, NSW, 2065
Ethics committee country [1] 308355 0
Australia
Date submitted for ethics approval [1] 308355 0
08/06/2020
Approval date [1] 308355 0
03/02/2021
Ethics approval number [1] 308355 0
2020_ETH01485

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110426 0
A/Prof Roderick Clifton-Bligh
Address 110426 0
Kolling Institute of Medical Research, Royal North Shore Hospital, Reserve Rd, St. Leonards, NSW, Australia, 2065
Country 110426 0
Australia
Phone 110426 0
+612 9926 4787
Fax 110426 0
Email 110426 0
[email protected]
Contact person for public queries
Name 110427 0
Roderick Clifton-Bligh
Address 110427 0
Kolling Institute of Medical Research, Royal North Shore Hospital, Reserve Rd, St. Leonards, NSW, Australia, 2065
Country 110427 0
Australia
Phone 110427 0
+612 9926 4787
Fax 110427 0
Email 110427 0
[email protected]
Contact person for scientific queries
Name 110428 0
Roderick Clifton-Bligh
Address 110428 0
Kolling Institute of Medical Research, Royal North Shore Hospital, Reserve Rd, St. Leonards, NSW, Australia, 2065
Country 110428 0
Australia
Phone 110428 0
+612 9926 4787
Fax 110428 0
Email 110428 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified patient data and data on efficacy and safety.
When will data be available (start and end dates)?
Start: 21 June 2021, no end date determined.
Available to whom?
This data will be published in relevant peer-reviewed journals and presented at conferences. If qualified researchers from other institutions request access to the data this will be considered in the future case by case.
Available for what types of analyses?
To achieve the aims in the approved proposal and for de-identified IPD meta-analyses.
How or where can data be obtained?
Access subject to approvals by Principal Investigator [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.