Personalized medicine for advanced biliary cancer patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jun 2024 → ongoing

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Zymeworks Inc. · Pierre Fabre Médicament · Accord Healthcare · TAIHO Inc. · Fondation contre le cancer (Belgian charity association) · Cancer Research UK (British charity association) · French Ministry of Health (PHRC) · GSK · Les laboratoires Servier

External identifiers

EU CT number

2023-508100-38-00

ClinicalTrials.gov

NCT05615818

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacogenomic

To evaluate whether maintenance treatment with MTTs to “actionable” targets (ESCAT I-III) after 4 cycles of 1L-SoC is superior to continuation of 1L-SoC in terms of progression-free survival (PFS).

Secondary objectives 6

1. To assess the efficacy of Precision oncology vs. 1L-SoC in ABC patients with ‘actionable’ tumour molecular alterations (ESCAT I-III)
2. To assess the efficacy of Each MTT (or MTT combination)
3. To assess the feasibility of molecular screening in a multinational, academic trial
4. To compare the health-related quality of life (HRQoL) of patients treated with MTTs vs. 1L-SoC
5. To assess the safety of the MTTs
6. To study prognostic value of molecular alterations, regardless of the randomisation

Conditions and MedDRA coding

Advanced Biliary Cancer (ABC)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 23

1. Screening phase - Signed a written informed consent form prior to any trial specific procedures (Consent #1)
2. Screening phase - Histologically-proven intrahepatic, perihilar or distal cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
3. Screening phase - De novo or recurrent, locally advanced (non-resectable) or metastatic disease
4. Screening phase - Availability of a suitable archived sample of primary or metastatic tumour tissue (frozen, or FFPE) or able to undergo a biopsy to obtain a suitable malignant tissue sample
5. Screening phase - Aged ≥18 years
6. Screening phase - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Screening phase - Estimated life expectancy >3 months
8. Screening phase - Candidate for 1L-SoC therapy, or has initiated first cycle of 1L-SoC therapy
9. Screening phase - Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements).
10. Randomised trial - Signed a written informed consent form prior to any trial specific procedures (Consent #2)
11. Randomised trial - Molecular profile showing the tumour harbours at least one targetable molecular alteration with a MTT in the study portfolio (as determined by the trial MTB)
12. Randomised trial - Disease control (stable or responsive) after 4 cycles of 1L-SoC, compared to a pretreatment disease evaluation, as assessed by the investigator
13. Randomised trial - ECOG performance status of 0 or 1
14. Randomised trial - Presence of at least one evaluable lesion according to RECIST v1.1, or complete response to 12 weeks 1L-SoC
15. Randomised trial - Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL
16. Randomised trial - Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range unless the patient has documented Gilbert syndrome, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN (AST and ALT ≤5 ULN when documented tumour liver involvement)
17. Randomised trial - Adequate renal function: estimated creatinine clearance ≥45 mL/min according to the Cockcroft-Gault formula
18. Randomised trial - Adequate cardiac function: left ventricular ejection fraction ≥50% at baseline as determined by either echocardiogram or multigated acquisition scan (MUGA)
19. Randomised trial - Adequate biliary drainage, with no evidence of ongoing infection
20. Randomised trial - Men, and women of childbearing potential (WOCBP) must agree to use adequate contraception for the duration of trial participation and as required after completing study treatment. Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.
21. Randomised trial - Women of childbearing potential must have a negative serum pregnancy test performed within 3 days before the date of randomisation
22. Randomised trial - Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures
23. Randomised trial - Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements)

Exclusion criteria 27

1. Screening phase - Contraindication to 1L-SoC
2. Screening phase - Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
3. Randomised trial - Disease progression occurring at any time prior randomisation, or toxicity that led to the discontinuation of the 1L-SoC before 4 full cycles have been delivered
4. Randomised trial - Toxicities from 1L-SoC not resolved to Grade ≤ 2 (according to version 5.0 the National Cancer Institute - Common terminology criteria for adverse events [NCI-CTCAE v5.0]) before randomisation, with the exception of alopecia
5. Randomised trial - Contraindication or known hypersensitivity to the MTT for the molecular alteration found in the patient, or any component in their formulation
6. Randomised trial - (MSI-H) or (dMMR) cancers
7. Randomised trial - Major surgery within 4 weeks of randomisation
8. Randomised trial - Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed
9. Randomised trial - Known leptomeningeal disease. If leptomeningeal disease has been reported radiographically on baseline magnetic responance imaging (MRI), but is not suspected clinically by the investigator, the subject must be free of neurological symptoms.
10. Randomised trial - Concurrent malignancy (other than ABC), with the exception of adequately treated conebiopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
11. Randomised trial - Known active hepatitis B virus or hepatitis C virus infection or human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
12. Screening phase - Individuals deprived of liberty or placed under protective custody or guardianship
13. Randomised trial - Any condition which in the Investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
14. Randomised trial - Women who are pregnant or breast-feeding
15. Randomised trial - Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable
16. Randomised trial - Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
17. Randomised trial - Individuals deprived of liberty or placed under protective custody or guardianship
18. For patients assigned to receive oral therapies - Inability or unwillingness to swallow pills
19. For patients assigned to receive oral therapies - History of malabsorption syndrome or other condition that would interfere with enteral absorption.
20. Screening phase - Patients who are candidates for locoregional therapy
21. Screening phase - Contraindication to tumour biopsy in the absence of suitable archived sample of tumour tissue
22. Screening phase - Prior anticancer therapy in the palliative setting. Adjuvant capecitabine allowed if completed ≥ 183 days prior to study entry
23. Screening phase - Received more than 1 cycle of treatment with 1L-SoC
24. Screening phase - Prior treatment with any of the MTT under investigation in the SAFIR-ABC10 study
25. Screening phase - Current malignancies (other than ABC), with the exception of adequately treated conebiopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 5 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
26. Screening phase - Any condition which in the Investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
27. Screening phase_Known microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancer at study entry

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival defined as the time from randomisation to the first documented progression of disease (PD) as assessed by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Patients alive and free of progression at the cut-off date will be censored at the last assessment date.

Secondary endpoints 5

1. Overall Survival (OS), defined as the time from randomisation to death due to any cause. Patients alive at the cut-off date will be censored on the last date the patient was known to be alive or lost to follow-up or withdraw consent.
2. Objective response rate, defined as the proportion of patients achieving CR or partial response (PR) as assessed by the investigator according to RECIST v1.1. Objective response rate will be presented as the best response achieved compared to the disease assessment performed at randomisation.
3. Time to treatment failure, defined as the time from patient starting their allocated treatment to the date at which a patient first experiences a treatment failure event.
4. Progression-free survival after next line of treatment (PFS2), defined as the time from randomisation to the date of second progression or death, whichever occurs first. Patients alive and free of second progression at the cut-off date will be censored at the last assessment date.
5. Duration of response, defined as the time from first documented PR or CR (compared to baseline measurement taken at randomisation) until the date of PD, as assessed by the investigator according to RECIST v1.1, or death from any cause whichever occurs first. Patients who are alive and have not progressed at the time of the analysis will be censored at their last evaluable tumour assessment.

Investigational products

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

Test 8

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Public contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Locations

2 EU/EEA countries · 52 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 53 files

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

Application history

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