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Resectable Intrahepatic CholangiocarcinomaPhase 2NCT05514912

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

A Phase 2 study testing Cisplatin, Gemcitabine Hydrochloride and Infigratinib Phosphate in people with Resectable Intrahepatic Cholangiocarcinoma and Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8, run by Emory University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cisplatin, Gemcitabine Hydrochloride and Infigratinib Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Mar 2024to 23 Jun 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Creatinine =< 1.5 x ULN
  • Have amylase or lipase < 2.0 x ULN
  • Male, or a non-pregnant and non-lactating female
  • Women of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must commit to true abstinence from heterosexual contact, or agree to use, and be able to comply with, effective contraception without interruption for 28 days prior to starting gemcitabine/cisplatin/nab- paclitaxel (including dose interruptions) until treatment with gemcitabine/cisplatin/nab-paclitaxel is complete.
  • Male subjects must practice true abstinence or agree to use a condom during sexual contact with a female of childbearing potential or a pregnant female while on treatment (including during dose interruptions) with gemcitabine/cisplatin/nab-paclitaxel and for 6 months following gemcitabine/cisplatin/nab- paclitaxel is continuation, even if he has undergone a successful vasectomy.

Who cannot join

  • 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:
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  • 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.
  • Previous (within the past 3 years) or concurrent presence of other cancer, except non-melanoma skin cancer, renal cell carcinoma < 3cm, neuroendocrine tumors < 2cm, and in situ carcinomas including bronchoalveolar carcinoma (BAC).
  • History of allergy or hypersensitivity to any of the study drugs.
  • Current abuse of alcohol or illicit drugs.
  • Inability or unwillingness to sign the informed consent form.

About this study

Official title: Optimal Preoperative Therapy for Intrahepatic Cholangiocarcinoma (OPTIC)

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the feasibility of a novel treatment strategy that includes conducting next generation sequencing (NGS)-based treatment on a preoperative tissue biopsy and subsequent administration of infigratinib phosphate (infigratinib) to patients with FGFR2 fusions versus neoadjuvant chemotherapy consisting of gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel to all other patients for resectable intrahepatic cholangiocarcinoma.

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of the intervention by assessing the radiological response rate.

II. To assess degree of pathologic response in the surgical specimen. III. To assess response to therapy by measuring circulating tumor deoxyribonucleic acid (CT-DNA).

IV. To determine the R0 resection rate. V. To determine recurrence-free survival (RFS). VI. To determine overall survival (OS).

OUTLINE:

While awaiting NGS molecular profile results, all patients receive nab-paclitaxel intravenously (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.

After obtaining NGS molecular profile results, patients who are FGFR2 fusion/translocation positive are assigned to Arm A, while patients who are FGFR2 fusion/translocation negative are assigned to Arm B.

ARM A: Patients receive infigratinib orally (PO) once daily (QD) on 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.

ARM B: Patients 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.

After completion of study treatment, patients are followed up within 4 weeks and every 4 months for 3 years.

Being tested
Cisplatin, Gemcitabine Hydrochloride, Infigratinib Phosphate, Nab-paclitaxel
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called dFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832

    Given IV

  • Infigratinib PhosphateDrug

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

    Given PO

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

Study groups in NCT05514912
Study groupRoleWhat they receive
Arm A (nab-paclitaxel, cisplatin, gemcitabine, infigratinib)ExperimentalWhile 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.
Receives: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Infigratinib Phosphate; Drug: Nab-paclitaxel
Arm B (nab-paclitaxel, cisplatin, gemcitabine)Active comparatorWhile 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.
Receives: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Drug: Nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 years

  2. 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.

    Measured: Up to 3 years

  3. 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.

    Measured: Up to 3 years

Secondary outcomes (5)

  1. Radiological Response Rate by Response Evaluation Criteria in Solid Tumors

    Radiological response rate will be defined as the percentage of patients who will have complete response, partial response or stable disease after the neoadjuvant therapy. The radiological response rate will be estimated, along with the exact 95% binomial confidence interval.

    Measured: Up to 3 years

  2. Pathologic Response Rate

    Pathologic response will be defined as the degree of treatment effect to preoperative therapy. This will be measured as percent of viable cancer cells and percent of necrotic cells in the surgically resected specimen. A pathologic complete response is defined as having no viable cancer cells in the surgical specimen at the time of surgery.

    Measured: Up to 3 years

  3. Circulating Tumor Deoxyribonucleic Acid Response

    Circulating tumor deoxyribonucleic acid will be collected as an exploratory secondary endpoint. The investigators will be blinded as to the results of the circulating tumor deoxyribonucleic acid assay until after the study is complete as to avoid any bias towards treatment decisions based on this exploratory endpoint.

    Measured: Up to 3 years

  4. Recurrence-Free Survival

    Recurrence-free survival is defined as the time between the date of surgery and the date of disease recurrence or death, whichever occurred first. If a patient did not have an event (i.e. disease recurrence or death) by the time of final analysis, patient will be censored at the last disease evaluation time. The Kaplan-Meier method will be used to estimate recurrence-free survival. The two-sided log-rank tests will be used to assess the differences of recurrence-free survival between groups.

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

  5. Overall Survival

    Overall survival is defined as the 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. If a patient is alive by the time of final analysis, the patient will be censored at the last follow-up date. The Kaplan-Meier method will be used to estimate overall survival. The two-sided log-rank tests will be used to assess the differences of overall survival between groups.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Aug 2022
  2. Study start1 Mar 2024 (estimated)
  3. Primary completion23 Jun 2027 (estimated)
  4. Study completion23 Jun 2027 (estimated)

Why it stopped: PI has decided to terminate this study due to study supporter pulling support on this study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05514912
Sponsor's protocol ID
STUDY00004206
Other IDs
NCI-2022-05975, STUDY00004206, WINSHIP5569-22, P30CA138292
Status last verified
Dec 2023
First submitted
19 Aug 2022
Last updated
26 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, Gemcitabine Hydrochloride and Infigratinib Phosphate in people with Resectable Intrahepatic Cholangiocarcinoma and Stage 0 Intrahepatic Cholangiocarcinoma AJCC v8, run by Emory University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 26 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of Completing All Preoperative Testing and Therapy (time frame: Up to 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05514912.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2023.

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