Preoperative Nab-paclitaxel, Cisplatin, and Gemcitabine Chemotherapy With or Without Infigratinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, The OPTIC Trial

NCT05514912 | Withdrawn Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00004206NCI-2022-05975WINSHIP5569-22P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial assesses the feasibility (including both safety and tolerability) of conducting Next Generation Sequencing and administering targeted therapy (infigratinib) in the preoperative setting for patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Chemotherapy drugs, such as nab-paclitaxel, cisplatin, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy with infigratinib will bind to FGFR which can help stop tumor cell growth and cause tumor cell death. Giving chemotherapy and/or targeted therapy before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. If a molecular profiling test shows a genetic change called an FGFR2 fusion, patients receive both chemotherapy and targeted therapy while patients without a FGFR2 fusion just receive chemotherapy. Giving targeted therapy based on molecular profile testing results prior to attempted resection of an intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes.

Conditions

Resectable Intrahepatic Cholangiocarcinoma; Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8; Stage I Intrahepatic Cholangiocarcinoma AJCC v8; Stage II Intrahepatic Cholangiocarcinoma AJCC v8; Stage III Intrahepatic Cholangiocarcinoma AJCC v8

Outcome Measures

Primary Outcomes (3)

• Feasibility of Completing All Preoperative Testing and Therapy

  Treatment completion is defined as completion of next generation sequencing testing and all preoperative and operative therapy. The completion of all therapy rate, along with the exact 95% binomial confidence interval will be record. If a patient is not a candidate for surgery after completion of all preoperative therapy, this will be considered an event against feasibility of this treatment strategy, at which time patients will receive further treatment as best deemed by their treating physician.

  Up to 3 years

• Unacceptable Toxicity

  Unacceptable toxicity is defined as any grade 3 or higher toxicities by Common Terminology Criteria for Adverse Events criteria that result in a treatment delay of \>4 weeks. The rate of unacceptable toxicity will be reported, along with the exact 95% binomial confidence interval. If the therapy cannot be completed due to a delay of \>4 weeks, this will be considered an event for this approach not being feasible.

  Up to 3 years

• Safety and Tolerability

  Safety and tolerability will be assessed in terms of adverse events, and serious adverse events. Summary of these events will be tabulated by the maximum reported Common Terminology Criteria for Adverse Events grade and in relation to study treatment. Both adverse Events and serious adverse events will be tabulated using frequencies and percentages.

  Up to 3 years

Secondary Outcomes (5)

• Radiological Response Rate by Response Evaluation Criteria in Solid Tumors

  Up to 3 years

• Pathologic Response Rate

  Up to 3 years

• Circulating Tumor Deoxyribonucleic Acid Response

  Up to 3 years

• Recurrence-Free Survival

  Time between the date of surgery and the date of disease recurrence or death, whichever occurred first, or assessed up to 3 years

• Overall Survival

  Time from date of neoadjuvant treatment start to the date of death from any cause or to the date of last follow-up if patients are alive, or assessed up to 3 years

Study Arms (2)

Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib)

EXPERIMENTAL

While awaiting NGS molecular profile results, all patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity. Patients who are FGFR2 fusion/translocation positive receive infigratinib PO QD for days 1-21 of each cycle. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients whose cancer is stable or improved undergo surgery to remove the tumor within 8 weeks of completing preoperative therapy per standard of care.

Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Infigratinib Phosphate; Drug: Nab-paclitaxel

Arm B (nab-paclitaxel, cisplatin, gemcitabine)

ACTIVE COMPARATOR

While awaiting NGS molecular profile results, all patients receive nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity. Patients who are FGFR2 fusion/translocation negative continue receiving nab-paclitaxel IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients whose cancer is stable or improved undergo surgery to remove the tumor within 8 weeks of completing preoperative therapy per standard of care.

Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Nab-paclitaxel

Interventions

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib); Arm B (nab-paclitaxel, cisplatin, gemcitabine)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011

Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib); Arm B (nab-paclitaxel, cisplatin, gemcitabine)

Infigratinib Phosphate DRUG

Given PO

Also known as: N'-(2,6-Dichloro-3,5-dimethoxyphenyl)-N-(6-(4-(4-ethylpiperazin-1-yl)anilino)pyrimidin-4-yl)-N-methylurea Phosphate (1:1), Truseltiq

Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib)

Nab-paclitaxel DRUG

Given IV

Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, Protein-bound Paclitaxel

Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib); Arm B (nab-paclitaxel, cisplatin, gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of intrahepatic cholangiocarcinoma
• High-quality cross-sectional imaging by computerized tomography (CT) or magnetic resonant imaging (MRI) performed within 6 weeks prior to enrollment and showed a resectable IHCCA confined to the liver, bile duct, and /or regional lymph nodes. No distant extrahepatic disease is allowed.
• Adults \> 18 years of age
• Able to give informed consent
• Able to adhere to study visit schedule and other protocol requirements
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate bone marrow reserves as evidenced by:
• Absolute neutrophil count (ANC) ≥1,500 cells/ul
• Platelet count ≥100,000 cells/μl
• Hemoglobin ≥9 g/dL
• Adequate hepatic function as evidenced by:
• Serum total bilirubin ≤1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN
• Albumin ≥3 g/dl
• Adequate renal function as evidenced by creatinine ≤1.5 x ULN

You may not qualify if:

• Peripheral neuropathy of grade 2 or greater by Common Terminology Criteria for Adverse Events (CTCAE) 4.0. In CTCAE version 4.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)".
• Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis, confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
• Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.
• Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
• Have current evidence of concerning endocrine alterations of calcium/phosphate homeostasis, eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc, in the opinion of the investigator.
• Have abnormal calcium or phosphorus, or calcium-phosphorus product ≥55 mg\^2 /dL2:
• Inorganic phosphorus above local normal limits
• Total corrected serum calcium above local normal limits
• Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
• Have clinically significant cardiac disease including any of the following: a. Congestive heart failure requiring treatment (New York Heart Association Grade ≥2), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines (Williams et al 2018)
• Fridericia's correction formula QTcF \>470 msec (males and females). Note: If the QTcF is \>470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the subject meets eligibility in this regard
• Known history of congenital long QT syndrome
• Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study such as unstable angina, myocardial infarction within 6 months, unstable symptomatic arrhythmia, symptomatic congestive heart failure, uncontrolled diabetes, serious active, uncontrolled infection after inadequate biliary drainage if tumor obstructing bile duct, or psychiatric illness/social situations.
• Pregnancy (positive pregnancy test) or lactation.
• Known CNS disease, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; infigratinib; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations

Study Officials

• Shishir K. Maithel, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 25, 2022
• Study Start: March 1, 2024
• Primary Completion (Estimated): June 23, 2027
• Study Completion (Estimated): June 23, 2027
• Last Updated: December 26, 2023

Record last verified: 2023-12