Trial Title:
Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation
NCT ID:
NCT06501625
Condition:
Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Conditions: Official terms:
Cholangiocarcinoma
Gemcitabine
Durvalumab
Ivosidenib
Antibodies, Monoclonal
Glycine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ivosidenib
Description:
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously
throughout treatment duration
Arm group label:
Safety Lead-In Phase
Intervention type:
Drug
Intervention name:
Durvalumab (for the first 8, 21-day, cycles)
Description:
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles
Arm group label:
Expansion Phase
Arm group label:
Safety Lead-In Phase
Intervention type:
Drug
Intervention name:
Gemcitabine (for the first 8, 21-day, cycles)
Description:
1000 mg/m2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles
Arm group label:
Expansion Phase
Arm group label:
Safety Lead-In Phase
Intervention type:
Drug
Intervention name:
Cisplatin (for the first 8, 21-day, cycles)
Description:
25 mg/m^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles
Arm group label:
Expansion Phase
Arm group label:
Safety Lead-In Phase
Intervention type:
Drug
Intervention name:
Durvalumab (starting from cycle 9)
Description:
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days
long, starting Cycle 9.
Arm group label:
Expansion Phase
Arm group label:
Safety Lead-In Phase
Intervention type:
Drug
Intervention name:
Ivosidenib Recommended Combination Dose (RCD)
Description:
RCD administered orally once daily, taken continuously throughout treatment duration
Arm group label:
Expansion Phase
Summary:
The objective of this study is to investigate the safety, tolerability and preliminary
activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as
first-line therapy in participants with locally advanced, unresectable or metastatic
cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in
phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will
transition to an expansion phase (Phase 2 study) to assess the clinical activity of
ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During
the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1,
on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through
8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90
days after treatment has ended, safety follow-up visits will occur and then participants
will be followed for survival every 3 months. Study visits may include blood tests, ECG,
vital signs, and a physical examination.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Have a histopathological confirmed diagnosis consistent with locally advanced
unresectable or metastatic cholangiocarcinoma.
- Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central
laboratory testing (R132C/L/G/H/S mutation variants tested).
- Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
- Have adequate bone marrow function as evidenced by:
- Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/mm3 or 100 × 109/L
- Have adequate hepatic function as evidenced by:
- Serum bilirubin ≤ 2.0 × the upper limit of normal (ULN); this will not apply to
patients with confirmed Gilbert's syndrome. Any clinically significant biliary
obstruction should be resolved before randomization
- Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
for patients with hepatic metastases, ALT and AST ≤ 5.0 × ULN
- Have adequate renal function, defined as: creatinine clearance > 60 mL/min per 24
hour urine or as calculated on the Cockcroft-Gault formula (using actual body
weight):
Creatine CL (mL/min)= (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum
creatinine (mg/dL)
Exclusion Criteria:
- Received treatment for locally advanced, unresectable or metastatic disease with the
following exceptions:
- Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is
permitted before study participation. Note: For the Safety Lead-In Phase,
participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin
and required dose modifications for treatment-related toxicity are excluded.
- Patients who developed recurrent disease > 6 months after surgery with curative
intent, and, if given, > 6 months after the completion of adjuvant (chemotherapy
and/or radiation).
- Prior exposure to immune-mediated therapy, including, but not limited to,
anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding
therapeutic anticancer vaccines.
- Unresolved Grade ≥2 adverse events from a previous anticancer therapy, with the
exception of alopecia and vitiligo and the laboratory values listed in the inclusion
criteria.
- Patients with Grade ≥2 neuropathy to be evaluated on a case-by-case basis after
consultation with the medical monitor
- Patients with irreversible toxicity not reasonably expected to be exacerbated by
treatment with ivosidenib may be included only after consultation with the medical
monitor
- Participation in another interventional study at the same time or within 14 days
prior to the first study medication (triple combination treatment) administration.
For patients having participated to another prior interventional study, the first
dose of ivosidenib should occur after a period greater than or equal to 5 half-lives
or 28 days, whichever is shorter of the last dose of the prior investigational
product.
- Active or prior documented autoimmune or inflammatory disorders including:
- inflammatory bowel disease (e.g., colitis or Crohn's disease)
- diverticulitis (with the exception of diverticulosis)
- systemic lupus erythematosus
- Sarcoidosis syndrome
- Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc.)
Note: in cases with no active disease for ≥ 5 years, patients may be considered for
inclusion if approved by the Medical Monitor. Participants with the following conditions
are eligible for the study:
- chronic skin condition that does not require systemic therapy
- vitiligo
- alopecia
- hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
therapy
- unmedicated celiac disease that is controlled by diet
- Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of ≥ 450
msec or with other factors that increase the risk of QT prolongation or arrhythmic
events (e.g., heart failure, hypokalemia, family history of long QT interval
syndrome/sudden death, polymorphic ventricular arrhythmia). The Sponsor should
review participants with bundle branch block and prolonged QTcF for potential
inclusion.
- Have an active infection, including:
- Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen
[HBsAg] and/or anti-HBcAb with detectable hepatitis B virus [HBV] DNA ≥ 10 IU/mL)
- Hepatitis C
- Tuberculosis (clinical evaluation includes: clinical history, physical examination
and/or radiographic findings, and tuberculosis testing as per local practice)
- Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2
antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) do not need to be
excluded from the study. Patients positive for hepatitis C (HCV) antibody are
eligible only if the polymerase chain reaction is negative for HCV RNA.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 16, 2024
Completion date:
January 15, 2030
Lead sponsor:
Agency:
Institut de Recherches Internationales Servier
Agency class:
Other
Source:
Servier
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06501625
