Safe Stop Trial Melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Dec 2024 → ongoing

Decision date (initial)

2024-12-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516937-10-01

EudraCT number

2018-001384-23

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this study is the rate of ongoing response in patients with advanced and metastatic melanoma who discontinue first-line monotherapy with nivolumab or pembrolizumab upon achieving a CR or PR.

Secondary objectives 20

1. The second objectives of this study include te evaluation of: 1. Duration of response after discontinuation of PD-1 blockade
2. The second objectives of this study include te evaluation of: 2. Outcome of patients after discontinuation of PD-1 blockade
3. The second objectives of this study include te evaluation of: 3. Need and feasibility of rechallenge of PD-1 blockade
4. The second objectives of this study include te evaluation of: 4. Disease control after rechallenge of PD-1 blockade
5. The second objectives of this study include te evaluation of: 5. Outcome of patients after rechallenge of PD-1 blockade
6. The second objectives of this study include te evaluation of: 6. Overall outcome after discontinuation and rechallenge of PD-1 blockade
7. The second objectives of this study include te evaluation of: 7. Impact of treatment discontinuation on AEs
8. The second objectives of this study include te evaluation of: 8. Change in tumor burden since start and after discontinuation of PD-1 blockade
9. The second objectives of this study include te evaluation of: 9. Change in QoL after discontinuation of PD-1 blockade measured at different time points
10. The second objectives of this study include te evaluation of: 10. Impact of early discontinuation of PD-1 blockade on fear of disease recurrence/progression
11. The second objectives of this study include te evaluation of: 11. Impact of early discontinuation of PD-1 blockade on productivity with respect to paid and unpaid work
12. The second objectives of this study include te evaluation of: 12. Impact of early discontinuation of PD-1 blockade on healthcare resource
13. The second objectives of this study include te evaluation of: 13. Impact of early discontinuation of PD-1 blockade on hours of informal care
14. The second objectives of this study include te evaluation of: 14. Changes in QoL at disease progression and restart of systemic therapy (when applicable)
15. The second objectives of this study include te evaluation of: 15. Changes in QoL in relation with tumor response
16. The second objectives of this study include te evaluation of: 16. Changes in QoL in relation with toxicity
17. The second objectives of this study include te evaluation of: 17. Changes in QoL in relation with number of hospital visits
18. The second objectives of this study include te evaluation of: 18. Differences in QoL in this trial as compared to QoL of patients without early discontinuation of PD-1 blockade
19. The second objectives of this study include te evaluation of: 19. Differences in productivity loss in this trial as compared to productivity loss of patients without early discontinuation of PD-1 blockade
20. The second objectives of this study include te evaluation of: 20. Changes in QoL after discontinuation of radiological follow-up

Conditions and MedDRA coding

Melanoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 year
2. Advanced or metastatic melanoma
3. Current treatment with first-line nivolumab or pembrolizumab for advanced or metastatic melanoma; previous systemic treatment, including immunotherapy, in (neo)adjuvant setting for resectable melanoma is allowed
4. Documented target lesion(s) according to RECIST v1.1 on diagnostic CT at start of PD-1 blockade with nivolumab or pembrolizumab
5. Documented tumor response evaluation every 12±1 weeks according to RECIST v1.1 (35) using a diagnostic CT as per standard practice
6. Presence of MRI brain for the screening of brain metastases (prior to discontinuation of PD-1 blockade)
7. Willingness to discontinue nlvolumab or pembrolizumab within 6 (+1) weeks weeks after confirmation of CR or PR before the full period of 2 years therapy

Exclusion criteria 1

1. Concomitant systemic therapies with other anti-cancer agents, e.g. BRAF-inhibitor, anti-CTLA4 (e.g. ipilimumab), or other PD-1 blockade than nlvolumab or pembrollzumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is the rate of ongoing responses (CR and PR) according to RECIST v1 .1 (35) at 24 months after first start of nivolumab/pembrolizumab

Secondary endpoints 20

1. 1a. Total duration of tumor response after first documented CR or PR followed by treatment interruption
2. 1 b. Duration of tumor response (CR and PR) after discontinuation of PD-1 blockade
3. 2. PFS from start of first-line monotherapy with PD-1 blockade (i.e. nivolumab or pembrolizumab) until first PD (PFS1)
4. 3a. Rate of reintroduction of monotherapy with PD-1 blockade (i.e. nivolumab or pembrolizumab) upon first PD
5. 3b. Rate of introduction of other systemic salvage therapy (i.e. other than monotherapy PD-1 blockade) upon first PD
6. 4a. Best tumor response on rechallenge with monotherapy PD-1 blockade (i.e. nivolumab or pembrolizumab)
7. 4b. Best tumor response after introduction of other systemic salvage therapy (i.e. other than monotherapy PD-1 blockade)
8. Sa. PFS after reintroduction of monotherapy PD-1 blockade (i.e. nivolumab, or pembrolizumab) (PFS2a)
9. Sb. PFS after introduction other systemic salvage therapy (i.e. other than monotherapy PD- 1 blockade) (PFS2b)
10. 6a. Total PFS (PFSTata1) defined as the period from initial start of PD-1 blockade until final PD (including period after discontinuation and (re-)introduction of nivolumab/ pembrolizumab or other salvage therapy)
11. Totale PFS gedefinieerd als de periode vanaf de eerste start van PD-1-blokkering tot de uiteindelijke PD (inclusief periode na staken en bij (her)start van nivolumab/pemprolizumab of andere systemische therapie (PFStotaal)
12. 7. Rate of grade 3-4 AEs after early discontinuation or reintroduction of nivolumab/pembrolizumab monotherapy
13. 8. Change in tumor burden since the start and after early discontinuation of PD-1 blockade
14. 9. Change in Qol after discontinuation of PD-1 blockade measured at different time point
15. 10. Change in fear of disease recurrence/progression
16. Change in productivity (paid and unpaid work) after discontinuation of PD-1 blockad
17. 12. Change in healthcare resource (within and outside the hospital) after discontinuation of PD-1 blockade
18. 13. Change in hours of informal care after discontinuation of PD-1 blockade
19. Qol at disease progression and restart of systemic therapy (when applicable)
20. 14. Verandering in Qol bij PD en herstart systemlsche theraple (indien van toepassing)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

dr. A. v.d. Veldt

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

dr. A. v.d. Veldt

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications