Does adding progesterone to dexamethasone in patients with brain swelling caused by cancer allow the use of lower doses of dexamethasone in the future?

PROgesterone as a Steroid SParing agent against oEdema occurring with secondary bRain cancers (PROSSPER)

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN16167828

Enrollment

Registered

2022-02-24

Start date

2022-10-20

Completion date

Unknown

Last updated

2024-09-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Oedema occurring with secondary brain cancers Cancer

Interventions

Current interventions as of 27/02/2024: Stage 1: Participants will receive a single oral dose of micronised progesterone 200 mg on Day 1 and a second single 600 mg dose 5 -21 days later. Blood samples

participants will also be asked to complete questionnaires and an interview. Previous interventions: Stage 1: Participants will receive a single oral dose of micronised progesterone 200 mg on Day 1 a

participants will also be as

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Current participant inclusion criteria as of 27/02/2024: 1. Patients =18 years old 2. Capable of giving informed consent 3. ECOG performance status 0, 1 or 2 4. Diagnosis of cerebral metastases 5. Receiving dexamethasone for control of brain tumour symptoms 6. Ability to swallow oral medication Previous participant inclusion criteria: 1. Patients =18 years old 2. Capable of giving informed consent 3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 4. Clinical and/or radiological diagnosis of cerebral metastases with peri-tumoural oedema on CT/MRI in the last 14 days 5. Responding symptomatically to dexamethasone for control of brain tumour symptoms at a dose of >8 mg for >48 hours 6. Ability to swallow oral medication

Exclusion criteria

Exclusion criteria: Current participant exclusion criteria as of 27/02/2024: 1. Patients who are unable or unwilling to give informed consent 2. History of unexplained vaginal bleeding 3. Concurrent meningioma 4. On HRT medication 5. History of cholestasis in the last 6 months 6. History of allergy to either progesterone or other ingredients of the trial drug including peanut allergy 7. Pregnant or lactating (all female patients of childbearing age will undergo pregnancy testing enrolment (Stage 1)/ randomisation (Stage 2) 8. Clinically significant co-morbidities that in the opinion of the investigator would preclude study participation 9. * Planned surgery, chemotherapy, or radiotherapy within the study treatment period *Stage 2 only. In Stage 1 there is no tumour assessment so the second micronized progesterone dose (with dexamethasone and pharmacokinetic sampling) can be after any local treatment provided the interval between trial dosing days is no more than 21 days 10. Patients participating in Stage 1 will not be eligible for Stage 2 Previous participant exclusion criteria: 1. Patients who are unable or unwilling to give informed consent 2. History of unexplained vaginal bleeding 3. Concurrent meningioma 4. On HRT medication 5. History of venous thromboembolic disease, myocardial infarction or stroke in last 12 months 6. History of cholestasis in the last 6 months 7. History of allergy to either progesterone or other ingredients of the trial drug including peanut allergy. 8. Pregnant or lactating (all female patients of childbearing age will undergo pregnancy testing prior to randomisation) 9. Clinically significant co-morbidities that in the opinion of the investigator would preclude study participation 10. Planned surgery, chemotherapy or radiotherapy within the 14-day study treatment period 11. Patients participating in Stage 1 will not be eligible for Stage 2

Design outcomes

Primary

Measure	Time frame
Current primary outcome measure as of 27/02/2024: Stage 1: >4 of 6 patients achieve a serum progesterone exposure (area under the concentration/time curve) of 50 – 150% of the target exposure. This will be measured in each patient on two occasions (day 1 and another day between days 5-21) using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations in eight timed blood samples. Stage 2: 1. >13 of 18 patients able to tolerate micronised progesterone until the end of the 14-day treatment period at a dose predicted to achieve the target progesterone exposure. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough). 2. Trough progesterone concentrations within 50 – 150% of target. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough) Previous primary outcome measure: Stage 1: >4 of 6 patients achieve a serum progesterone exposure (area under the concentration/time curve) of 50 – 150% of the target exposure. This will be measured in each patient on two occasions (day 1 and another day between days 5-10) using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations in eight timed blood samples. Stage 2: 1. >13 of 18 patients able to tolerate micronised progesterone until the end of the 14-day treatment period at a dose predicted to achieve the target progesterone exposure. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough). 2. Trough progesterone concentrations within 50 – 150% of target. This will be measured in each patient on days 1, 8 a	—

Measure

Time frame

Current primary outcome measure as of 27/02/2024: Stage 1: >4 of 6 patients achieve a serum progesterone exposure (area under the concentration/time curve) of 50 – 150% of the target exposure. This will be measured in each patient on two occasions (day 1 and another day between days 5-21) using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations in eight timed blood samples. Stage 2: 1. >13 of 18 patients able to tolerate micronised progesterone until the end of the 14-day treatment period at a dose predicted to achieve the target progesterone exposure. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough). 2. Trough progesterone concentrations within 50 – 150% of target. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough) Previous primary outcome measure: Stage 1: >4 of 6 patients achieve a serum progesterone exposure (area under the concentration/time curve) of 50 – 150% of the target exposure. This will be measured in each patient on two occasions (day 1 and another day between days 5-10) using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations in eight timed blood samples. Stage 2: 1. >13 of 18 patients able to tolerate micronised progesterone until the end of the 14-day treatment period at a dose predicted to achieve the target progesterone exposure. This will be measured in each patient on days 1, 8 and 14 using liquid chromatography-triple quadrupole mass spectrometry (LC/MS/MS) to estimate drug concentrations, each at a single timepoint (Ctrough). 2. Trough progesterone concentrations within 50 – 150% of target. This will be measured in each patient on days 1, 8 a

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Secondary

Measure	Time frame
Secondary outcome measures: 1. Compliance with the structured dexamethasone dose reduction guidelines at 75% of decision points in at least 13 of 18 patients in line with protocol guidelines and as clinically appropriate. This will be measured by comparing the actual timing of dexamethasone dose reduction to that planned in the protocol at the specified timepoints after each patient has completed stage 2 (22 days duration) 2. Description of dexamethasone-related symptoms and quality of life measured by completion of a patient diary (days 1-22) and the quality of life (QoL) questionnaires DSQ-C, EORTC QLQ-C30 and EORTC BN20 (day 1 and day 14) 3. Percentage of patients achieving a >50% reduction in dexamethasone dose taken on Day 14 , measured by comparing dexamethasone dose at Day 1 and Day 14 in the two patient groups (progesterone and placebo) 4. Comparison of final dexamethasone dose on Day 14 measured by comparing dexamethasone dose at Day 1 and Day 14 in the two patient groups (progesterone and placebo) Tertiary outcome measures: 1. Confirmation that patients on micronised progesterone have no additional clinically significant changes in their endocrine, liver function or lipid profile. This will be measured by comparison of laboratory data on Days 1, 8, 14 and 22 2. Description of changes on CT/MRI in patients on micronised progesterone compared to those on placebo. CT/MRI will be conducted at screening and Day 14 3. Acceptability/feasibility of PROMs and future trial design, including randomisation, established through patient interviews. This will be measured after each patient has completed stage 2 (22 days duration)	—

Measure

Time frame

Secondary outcome measures: 1. Compliance with the structured dexamethasone dose reduction guidelines at 75% of decision points in at least 13 of 18 patients in line with protocol guidelines and as clinically appropriate. This will be measured by comparing the actual timing of dexamethasone dose reduction to that planned in the protocol at the specified timepoints after each patient has completed stage 2 (22 days duration) 2. Description of dexamethasone-related symptoms and quality of life measured by completion of a patient diary (days 1-22) and the quality of life (QoL) questionnaires DSQ-C, EORTC QLQ-C30 and EORTC BN20 (day 1 and day 14) 3. Percentage of patients achieving a >50% reduction in dexamethasone dose taken on Day 14 , measured by comparing dexamethasone dose at Day 1 and Day 14 in the two patient groups (progesterone and placebo) 4. Comparison of final dexamethasone dose on Day 14 measured by comparing dexamethasone dose at Day 1 and Day 14 in the two patient groups (progesterone and placebo) Tertiary outcome measures: 1. Confirmation that patients on micronised progesterone have no additional clinically significant changes in their endocrine, liver function or lipid profile. This will be measured by comparison of laboratory data on Days 1, 8, 14 and 22 2. Description of changes on CT/MRI in patients on micronised progesterone compared to those on placebo. CT/MRI will be conducted at screening and Day 14 3. Acceptability/feasibility of PROMs and future trial design, including randomisation, established through patient interviews. This will be measured after each patient has completed stage 2 (22 days duration)

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Countries

England, United Kingdom

Contacts

Public ContactProssper Study Team

phs.prossper@phs.scot+44 (0)131 275 7058

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026