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Non-Resectable CholangiocarcinomaPhase 1NCT02856568

Ricolinostat, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable or Metastatic Cholangiocarcinoma

A Phase 1 study testing Cisplatin, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis in people with Non-Resectable Cholangiocarcinoma and Recurrent Cholangiocarcinoma, run by Mayo Clinic at 3 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase Ib trial studies the side effects and best dose of ricolinostat when given together with gemcitabine hydrochloride and cisplatin in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cisplatin, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesUnited States
Study dates
1 May 2017to Oct 2021
Phase
Phase 1
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

  • Histological or cytologic confirmation of unresectable or metastatic cholangiocarcinoma (intrahepatic, hilar, extrahepatic bile duct)
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1200/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin < 1.5 x upper limit of normal (ULN), If patient has known Gilbert's syndrome, direct bilirubin < 2.0 x ULN
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  • Aspartate transaminase (AST) =< 5 x ULN
  • Alkaline phosphatase =< 5 x ULN
  • Creatinine =< 1.5 x ULN
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Ability to complete a patient medication diary by themselves or with assistance
  • Provide informed written consent
  • Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willingness to provide tissue and blood samples for correlative research purposes
  • Life expectancy >= 3 months
  • Prior embolization, chemoembolization, or radiofrequency ablation permitted if >= 4 weeks from registration and evidence of new tumor growth is present

Who cannot join

  • Any of the following
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
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  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Central nervous system (CNS) metastasis; NOTE: history of brain metastasis other than locally treatable lesions (i.e., lesions treatable with surgery or radiosurgery); patients with locally treatable disease may be considered for study if they have completed treatment without evidence of CNS progression for > 4 weeks after completion of treatment; patients with a history of brain or other CNS metastases not amenable to local therapy will not be eligible
  • Prior biologic or immunologic therapy =< 4 weeks prior to study entry
  • Prior systemic chemotherapy for cholangiocarcinoma or gallbladder carcinoma; NOTE: adjuvant chemotherapy is allowed if completed > 6 months prior to the start of registration
  • Prior radiation of cholangiocarcinoma or gallbladder carcinoma; NOTE: adjuvant radiation therapy is allowed if completed > 6 months prior to the start of registration
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix or breast, or prostatic intraepithelial neoplasm; NOTE: if there is a history or prior malignancy, patient must not be receiving other specific treatment (other than hormonal therapy) for their cancer
  • History of myocardial infarction =< 6 months from registration, or congestive heart failure requiring use of ongoing maintenance therapy for life threatening ventricular arrhythmias

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase Ib, Open-Label, Dose- Escalation Trial of ACY-1215 in Combination With Gemcitabine and Cisplatin in Patients With Unresectable or Metastatic Cholangiocarcinoma

This phase Ib trial studies the side effects and best dose of ricolinostat when given together with gemcitabine hydrochloride and cisplatin in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places in the body. Ricolinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, 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. Giving ricolinostat together with gemcitabine hydrochloride and cisplatin may work better in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) or a dose up to 240 mg/day, whichever is lower, of ricolinostat (ACY-1215) in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Cohort I)

SECONDARY OBJECTIVES:

  1. Characterize the safety profile of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) II. Determine the single- and multiple-dose pharmacokinetic (PK) of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) III. To evaluate tumor response to treatment with ACY-1215 in combination with gemcitabine and cisplatin (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). (Both cohorts) IV. To assess progression-free and overall survival of patients treated with ACY-1215 in combination with gemcitabine and cisplatin. (Both cohorts)

TERTIARY OBJECTIVES:

  1. Both blood and tissue samples will be obtained at baseline and post-treatment cycle 2 for future biomarker development, analysis, and potential blood based molecular/genomic profiling. (Both cohorts) II. Studies on Tissue pre-cycle 1 and post-cycle 2 of therapy will include: phospho extracellular signal-regulated kinases (ERK)1/2; hedgehog-signaling pathways (Gli transcription factors); BIM; histones acetylation; acetylation alpha (a)-tubulin; histone deacetylase (HDAC)6 levels; autophagy markers heat shock protein (HSP)90/70; hypoxia-inducible factor 1 (HIF1)alpha; beclin; microtubule-associated proteins 1A/1B light chain 3 (LC3); Ras homolog gene family member B (RhoB).

OUTLINE: This is a dose-escalation study of ricolinostat.

Patients receive cisplatin intravenously (IV) followed by gemcitabine hydrochloride IV on days 1 and 8, and ricolinostat orally (PO) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

Being tested
Cisplatin, Gemcitabine Hydrochloride, Laboratory Biomarker Analysis, Pharmacological Study, Ricolinostat
Medical subject headings
Cholangiocarcinoma, Bile Duct Neoplasms, Klatskin Tumor

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, Gemzar, LY-188011

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • RicolinostatDrug

    Also called ACY-1215, Histone Deacetylase 6 InhibitorACY-1215

    Given PO

Study groups in NCT02856568
Study groupRoleWhat they receive
Treatment (cisplatin, gemcitabine hydrochloride, ricolinostat)ExperimentalPatients receive cisplatin IV followed by gemcitabine hydrochloride IV on days 1 and 8, and ricolinostat PO on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cisplatin; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Ricolinostat

What is being measured

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

  1. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: Cycle 1, Day 1 pre-dose

  2. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: Cycle 1, Day 8 pre-dose

  3. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 0.5 hr after ACY-1215 dosing

  4. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 24 hr after Cycle 1, Day 1 only

  5. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: Prior to Cycle 1, Day 2 ACY-1215 dosing

  6. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 1 hr after ACY-1215 dosing

  7. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 2hr after ACY-1215 dosing

  8. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 4 hr after ACY-1215 dosing

  9. MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215

    PK blood sample

    Measured: 6-8 hr after ACY-1215 dosing

Secondary outcomes (8)

  1. Best Response defined as the best objective status recorded using RECIST version 1.1

    Responses will be summarized by simple descriptive summary statistics.

    Measured: Up to 1 year

  2. Confirmed response is defined to be a stringent complete response, complete response, very good partial response, or partial response noted as the objective status on two consecutive evaluations using RECIST version 1.1

    Will be evaluated using all cycles of treatment. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group). The number of responses may indicate further evaluation for specific tumor types in a Phase II setting.

    Measured: Up to 1 year

  3. Incidence of adverse events evaluated via the ordinal common toxicity criteria (CTC) toxicity grading of 3+

    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 1 year

  4. Time to any hematologic nadirs (ANC, platelets, hemoglobin)

    Will be summarized descriptively.

    Measured: Up to 1 year

  5. Time to any treatment related grade 3+ toxicity

    Will be summarized descriptively.

    Measured: Up to 1 year

  6. Time to any treatment related toxicity

    Will be summarized descriptively.

    Measured: Up to 1 year

  7. Time to progression

    Will be summarized descriptively.

    Measured: From registration to documentation of progression, up to 1 year

  8. Time to treatment failure

    Will be summarized descriptively.

    Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient assessed up to 1 year

Timeline

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

  1. First posted5 Aug 2016 (estimated)
  2. Study start1 May 2017
  3. Primary completionOct 2021 (estimated)
  4. Study completionOct 2021 (estimated)

Why it stopped: Site dropped 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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02856568
Sponsor's protocol ID
MC1542
Other IDs
NCI-2016-01057, MC1542, P30CA015083
Status last verified
May 2017
First submitted
14 Jul 2016
Last updated
30 May 2017
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cisplatin, Gemcitabine Hydrochloride and Laboratory Biomarker Analysis in people with Non-Resectable Cholangiocarcinoma and Recurrent Cholangiocarcinoma, run by Mayo Clinic at 3 sites in United States.

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 16 inclusion and 14 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 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

MTD of ricolinostat or a dose up to 240 mg/day whichever is lower, of ACY-1215 (time frame: Cycle 1, Day 1 pre-dose). The study lists 9 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 NCT02856568.

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 30 May 2017.

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