An early access study of ivosidenib in patients with a pretreated locally advanced or metastatic cholangiocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Servier Affaires Medicales

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 May 2023 → ongoing

Decision date (initial)

2023-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

SERVIER AFFAIRES MÉDICALES

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Safety, Pharmacogenomic, Others, Efficacy

Safety of ivosidenib in patients with pretreated locally advanced or metastatic CCA

Secondary objectives 3

1. • Efficacy in daily clinical practice
2. • Quality of life (HRQOL)
3. • Utilization of medical resources

Conditions and MedDRA coding

Locally Advanced or Metastatic Cholangiocarcinoma

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Servier’s Data Sharing Policy is available at https://clinicaltrials.servier.com/data-request-portal/. Researchers can ask for a study protocol, patient-level and/or study-level clinical study data including clinical study reports. They can ask for all interventional clinical studies in patients: - submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). - where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, Servier’s data sharing policy includes all interventional clinical studies in patients: - sponsored by Servier - with a first patient enrolled as of 1 January 2004 onwards - for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any MA approval.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Be ≥18 years of age
2. 2. Have a histopathological diagnosis of CCA consistent with nonresectable or metastatic CCA and are not eligible for curative-intent resection, transplantation, or ablative therapies
3. 3. Have documented IDH1 R132C, R132L, R132G, R132H, or R132S gene-mutated disease based on a local validated biomolecular profiling method
4. 4. Have documented locally advanced or metastatic CCA following at least 1 prior line of systemic therapy
5. 5. Have an ECOG PS score of 0 or 1
6. 6. Have recovered from toxicities associated with prior anticancer therapy to baseline or have stabilized under medical management
7. 7. Have adequate bone marrow function as described in the protocol.
8. 8. Have adequate hepatic function as described in the protocol.
9. 9. Have adequate renal function as described in the protocol.
10. 10. Be able to understand and willing to sign the informed consent form (ICF) and to comply with the study procedures.
11. 11. Willingness to comply with contraception guidelines of this study.

Exclusion criteria 16

1. 1. Received a prior IDH1 inhibitor
2. 2. Had a prior transplantation
3. 3. Received systemic anticancer therapy <2 weeks prior to first dose of study treatment on C1D1, immune based anticancer therapy <4 weeks prior to C1D1, or an investigational agent <5 half-lives of this agent prior to C1D1
4. 4. Received radiotherapy to metastatic sites of disease <2 weeks prior to C1D1
5. 5. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to C1D1
6. 6. Have known symptomatic brain metastases requiring steroids.
7. 7. Have a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid or liquid tumor with no known active disease present that, in the opinion of the Investigator, will not affect patient outcome in the setting of current CCA diagnosis.
8. 8. Underwent major surgery <4 weeks prior to C1D1 or have not recovered from post-surgery toxicities
9. 9. Are pregnant or breastfeeding
10. 10. Are taking known strong cytochrome P450 (CYP) 3A4 inducers or inhibitors or sensitive CYP3A4 substrate medications, unless they can be transferred to other medications.
11. 11. Are taking P-glycoprotein (P-gp) transporter-sensitive substrate medications or inhibitors unless they can be transferred to other medications.
12. 12. Have an active infection requiring systemic anti-infective therapy or with an unexplained fever >38.5°C within 7 days of Day 1.
13. 13. Have any known hypersensitivity to any of the components of ivosidenib
14. 14. Have significant active cardiac disease within 6 months prior to the start of study treatment.
15. 15. Have known active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency syndrome (AIDS) related illness.
16. 16. Have any gastrointestinal medical condition which would limit ingestion or gastrointestinal absorption according to investigator’s judgment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. AEs, serious AEs (SAEs), AEs of special interest (AESIs), AEs leading to discontinuation or death, safety laboratory parameters, 12-lead ECG, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status (PS)

Secondary endpoints 5

1. • Response to treatment based on tumor assessments by the investigator according to local clinical practice o Progression-free survival (PFS) o Overall survival (OS) o Duration of response (DOR) o Time to response (TTR)
2. • HRQOL as assessed by the validated European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21)
3. • Health economic outcomes as assessed by the 5 level EuroQol 5-dimensional questionnaire (EQ-5D-5L)
4. • Proportion of days at home or hospital
5. • Concomitant medications

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Servier Affaires Medicales

Sponsor organisation

Servier Affaires Medicales

Address

35 Rue De Verdun

City

Suresnes Cedex

Postcode

92284

Country

France

Scientific contact point

Organisation

Servier Affaires Medicales

Contact name

Global Evidence Generation Lead

Public contact point

Organisation

Servier Affaires Medicales

Contact name

Global Evidence Generation Lead

Third parties 7

Locations

10 EU/EEA countries · 58 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 189 files

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

Application history

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