Ivosidenib in Locally Advanced or Metastatic Cholangiocarcinoma With IDH1 R132 Mutation After at Least One Prior Systemic Treatment - an Observational Study

Recruiting

• Conditions: Cholangiocarcinoma

• Registration Number: NCT06607302
• Lead Sponsor: iOMEDICO AG

Brief Summary

Cholangiocarcinoma is a rare and aggressive tumor of the bile duct associated with a poor prognosis and very limited treatment options. The IDH1 inhibitor ivosidenib provides a new, targeted treatment option for this disease. Ivosidenib was approved by European Medicines Agency (EMA) in May 2023 as monotherapy in adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.

The prospective, multicenter, observational study IDHIRA will collect first real-world data on ivosidenib treatment in a broad patient population in Germany. Ivosidenib will be administered according to the current SmPC. Thus, IDHIRA will generate real-world evidence on effectiveness, quality of life (QoL) and safety of ivosidenib.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-16
• Study First Submitted QC: 2024-09-18
• Study First Posted: 2024-09-23
• Study Start: 2024-10-08
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Age 18 years or older.

• Histologically confirmed locally advanced or metastatic CCC with a documented IDH1 R132 mutation diagnosed by an appropriate diagnostic test

• Patients must have at least one prior systemic therapy

• Decision for treatment with ivosidenib according to current SmPC.

• Signed written informed consent before or within 6 weeks of first ivosidenib dose (inclusion of patients up to 6 weeks after first ivosidenib intake is allowed for patients not participating in the PRO module)

• For patients participating in the PRO module (optional):

  • Dated signature of informed consent form before start of study treatment.
  • Willingness and capability to participate in PRO assessment in German language.

• Other criteria according to current SmPC.

Exclusion Criteria

• Participation in an interventional clinical trial within 30 days prior to enrolment or concurrent participation in an interventional clinical trial except for the follow-up period.
• Other contraindications according to current SmPC.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	max. 38 months (FPI - LPLV)	PFS is defined as the time interval measured from the day of first ivosidenib administration to first progression or death, whichever comes first. Patients without tumor progression or death at the time of analysis will be censored at their date of last contact.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	max. 38 months (FPI - LPLV)	OS is defined as the time interval measured from the day of first ivosidenib administration to time of death from any cause. Time to last contact will be used if a patient has no documented date of death and OS for the patient will be considered censored.
Timt to treatment failure (TTF)	max. 38 months (FPI - LPLV)	TTF is defined as the time interval measured from the day of first ivosidenib until discontinuation of treatment for any reason including progression, toxicity, start of a new antineoplastic therapy, or death, whichever occurs first. Patients dropping out without knowledge of a potential ending of therapy (e.g., lost to follow up) will be censored with the last date of contact.
Overall response rate (ORR)	max. 38 months (FPI - LPLV)	ORR is defined as the proportion of patients achieving a complete or partial response as best response. Patients without response measurement are considered non-responders.
Disease control rate (DCR)	max. 38 months (FPI - LPLV)	DCR is defined as the proportion of patients achieving complete response, partial response, or stable disease as best response. Patients without response measurement are considered non-responders.
(Serious) adverse drug reactions ((S)ADR) related to ivosidenib	max. 38 months (FPI - LPLV)	The case- and patient-based incidence of (S)ADRs will be provided.
Adverse events of special interest (AESI)	max. 38 months (FPI - LPLV)	The case- and patient-based incidence of AESIs will be provided.
Reasons for dose modifications	max. 38 months (FPI - LPLV)	Reasons for dose modifications will be presented.
Duration of treatment with ivosidenib	max. 38 months (FPI - LPLV)	Duration of treatment with ivosidenib
Reasons for end of treatment (EOT)	max. 38 months (FPI - LPLV)	Reasons for end of treatment will be displayed
Type of last previous therapy	max. 38 months (FPI - LPLV)	Type of substances given in the last previous therapy will be displayed.
(Serious) adverse events ((S)AE))	max. 38 months (FPI - LPLV)	The case- and patient-based incidence of (S)AEs will be provided.
Global health-related quality of life during course of treatment	max. 38 months (FPI - LPLV)	The change from baseline (i.e., difference) in the scales of the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30) will be displayed for each point in time, using boxplots.; The scales of the EORTC QLQ-C30 range in score from 0 to 100. A high scale score represents a higher response level.
Cholangiocarcinoma-related quality of life during course of treatment	max. 38 months (FPI - LPLV)	The change from baseline (i.e., difference) in the scales of the EORTC QLQ-BIL21 (European Organisation for Research and Treatment of Cancer quality of life questionnaire BIL21) will be displayed for each point in time, using boxplots.; The scales of the EORTC QLQ-BIL21 range in score from 0 to 100. A high scale score represents a higher response level.
Assessing parameters of physician treatment decision making	max. 30 months (recruitment period)	Frequencies of distinct impact ratings for parameters affecting ivosidenib therapy choice will be visualized using stacked bar charts.
Assessing parameters of physician treatment satisfaction	max. 32 months (recruitment period plus 8 weeks)	Frequencies of distinct satisfaction levels with ivosidenib treatment effectiveness and AE management will be visualized using stacked bar charts.
Cumulative ivosidenib dose	max. 38 months (FPI - LPLV)	Summary tables containing descriptive statistics (n, mean, standard deviation, median, 25th and 75th percentiles, minimum, and maximum) will be provided.
Absolute dose intensity of ivosidenib	max. 38 months (FPI - LPLV)	Summary tables containing descriptive statistics (n, mean, standard deviation, median, 25th and 75th percentiles, minimum, and maximum) will be provided.
Relative dose intensity of ivosidenib	max. 38 months (FPI - LPLV)	Summary tables containing descriptive statistics (n, mean, standard deviation, median, 25th and 75th percentiles, minimum, and maximum) will be provided.
Frequency of dose modifications	max. 38 months (FPI - LPLV)	Frequency of dose modifications will be presented.
Type of dose modifications	max. 38 months (FPI - LPLV)	Type of dose modifications (i.e., dose reductions, dose escalations, and interruptions) will be presented.
Frequency of last previous therapy	max. 38 months (FPI - LPLV)	Frequency of different substances given in the last previous therapy will be displayed.
Duration of last previous therapy line	max. 38 months (FPI - LPLV)	Duration of last previous therapy line will be displayed.
Concomitant medications	max. 38 months (FPI - LPLV)	Frequency of concomitant medications in total will be displayed.
Concomitant medications known to induce QT prolongation	max. 38 months (FPI - LPLV)	Frequency of concomitant medications known to induce QT prolongation (e.g., antiarrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) will be displayed.
Subsequent antineoplastic therapies	max. 38 months (FPI - LPLV)	Frequency and type of subsequent antineoplastic therapies by line of therapy will be displayed.

Trial Locations

Locations (2)

Caritas Krankenhaus Bad Mergentheim; 🇩🇪 Bad Mergentheim, Germany

Onkologisches Versorgungszentrum Berlin MVZ; 🇩🇪 Berlin, Germany