Inoperable Locally Advanced or Metastatic Biliary Tract CancerPhase 1NCT01949870

Selumetinib (AZD6244, ARRY-142886) J-BTC Phase 1 Study

A Phase 1 study testing Cisplatin, Gemcitabine and Selumetinib in people with Inoperable Locally Advanced or Metastatic Biliary Tract Cancer, run by AstraZeneca at 2 sites in Japan.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 20 to 130 years
Conditions the study is for: Inoperable Locally Advanced or Metastatic Biliary Tract Cancer
What is being tested?: Cisplatin, Gemcitabine and Selumetinib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 2 sitesJapan
Study dates: Oct 2013to Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 20 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of written informed consent
Patients must be ≥ 20 years
Histological or cytological confirmation of locally advanced or metastatic BTC (intra- or extra-hepatic, gallbladder or ampullary carcinoma)
Patients who are eligible for treatment with standard dose of cisplatin/gemcitabine combination regimen
World Health Organisation (WHO) performance status (PS) 0-1
Evidence of post-menopausal status or negative urine/serum pregnancy test for nonmenopausal female patients Women will be considered postmenopausal if they are amenorrheic for 1 year or more without an alternative medical cause. The following age-specific requirements apply: i) Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 1 year or more following cessation of exogenous hormonal treatments and with Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range.
Women over 50 years old would be consider postmenopausal if they have been amenorrheic for 1 year or more following cessation of all exogenous hormonal treatments, radiation-induced oophorectomy with last menses > 1 year ago, chemotherapy-induced menopause with >1 year interval since last menses. Or surgical sterilisation (bilateral oophorectomy or hysterectomy). 7. Male patients should be willing to use barrier contraception for a specified period 8. A lesion that can be accurately assessed at baseline by CT or magnetic resonance imaging (MRI) and is suitable for repeated assessment in accordance with RECIST 9. Patients must have a life expectancy ≥16 weeks 10. Patients who can remain in Hospital from Cycle 0 Day 1 up to at least the completion of Cycle 1 Day 9 11. Patient is willing to provide fresh or archival tumour sample and biomarker blood sample.
-

Who cannot join

Treatment with any of the following:
Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment
Chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
selumetinib(therefore, patients who have already participated in this study and been taken selumetinib) or any other MEK(Mitogen-activated protein kinase kinase or Mitogen-activated protein kinase (MAPK) / Extracellular signal-regulated kinase (ERK) kinase) 1/2 inhibitor in past
Cisplatin or gemcitabine in past

Show all 48Show fewer

Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment
With the exception of alopecia, any unresolved toxicities from prior therapy ≥Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, such as,
active bleeding diatheses
active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
severe renal impairment, uncontrolled diabetes or renal transplant
acute uncontrolled infection
current unstable or uncompensated respiratory or cardiac disease
peripheral vascular disease including diabetic vasculopathy Screening for chronic conditions is not required
Any of the following cardiac criteria:
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (eg, heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or mean resting corrected QT interval (QTc) > 470 msec)
Uncontrolled hypertension (BP≥150/95 mmHg despite medical therapy)
Acute coronary syndrome within 6 months prior to starting treatment
Angina Canadian Cardiovascular Society Grade II-IV (despite medical therapy)
Symptomatic heart failure (NYHA [New York Heart Association ] II-IV)
Prior or current cardiomyopathy
Baseline left ventricular ejection fraction (LVEF) <55% measured by echocardiography or Multiple Gated Acquisition Scan (MUGA)
Atrial fibrillation with a ventricular rate >100 bpm at rest
Severe valvular heart disease
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Absolute neutrophil count < 1.5 x 109/L
Platelet count < 100 x 109/L
Haemoglobin < 90 g/L
Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN)
Aspartate aminotransferase (AST) > 2.5 times ULN
Total bilirubin > 1.5 times ULN
Creatinine clearance < 50 mL/min (measured or calculated by Cockcroft and Gault equation)
Any of the following ophthalmological criteria:
Current or past history of central serous retinopathy or retinal vein occlusion
Intraocular pressure >21 mmHg
Uncontrolled glaucoma (irrespective of intraocular pressure)
Inadequate biliary drainage
Symptomatic patients with interstitial pneumonitis or lung fibrosis confirmed by plain chest X-ray or chest CT
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of selumetinib
History of hypersensitivity to selumetinib or drugs with a similar chemical structure or class to selumetinib
History of hypersensitivity to platinum and gemcitabine containing drugs
Use of strong CYP(Cytochrome P450)1A2, CYP(Cytochrome P450)2C19 or CYP3A4 inducers and/or inhibitors (for example, but not limited to, fluvoxamine, fluconazole, ticlopidine, ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nelfinavir, ritonavir, saquinavir,telithromycin, voriconazole, grapefruit and seville orange or the juices of these fruits, rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort)
Any contraindication to the combination chemotherapy as per local prescribing information
Judgment by the investigators that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site).

Trial locations and contacts

2 sites in 1 country.

Japan2 sites

AZD6244 PhI Japanese Gem/
Chuo Ku, Tokyo
AZD6244 PhI Japanese Gem/
Kashiwa Shi, Chiba

Other trials in Japan

About this study

Official title: A Phase I, Open-Label, Multi-Center Study to Assess the Safety and Tolerability of Selumetinib (AZD6244, ARRY-142886) in Combination With Cisplatin/Gemcitabine in Japanese Patients With Inoperable Locally Advanced or Metastatic Biliary Tract Cancer (BTC)

The objective of this study is to investigate the safety and tolerability of oral dose of selumetinib in combination with chemotherapies (cisplatin and gemcitabine) in Japanese patients with advanced biliary tract cancer (BTC). In addition, the pharmacokinetic (PK) profile of selumetinib and chemotherapies will be investigated. Also, the Maximum tolerated dose (MTD) of selumetinib in combination with chemotherapies for Japanese BTC patients will be identified, if possible.

Conditions: Inoperable Locally Advanced or Metastatic Biliary Tract Cancer
Being tested: Cisplatin, Gemcitabine, Selumetinib
Medical subject headings: Biliary Tract Neoplasms

What participants receive

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

CisplatinDrug
day1 and day8 at each cycle
GemcitabineDrug
day1 and day8 at each cycle
SelumetinibDrug
Also called AZD6244
25mg/day, 50mg/day and 75mg/day

Study groups in NCT01949870
Study group	Role	What they receive
Selumetinib	Other	25mg/day, 50mg/day and 75mg/day Receives: Drug: Cisplatin; Drug: Gemcitabine; Drug: Selumetinib

What is being measured

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

The Number of Dose-limiting Toxicities
The number of dose-limiting toxicities in selumetinib in combination with cisplatin and gemcitabine
Measured: The first cycle with selumetinib until Day 1 of Cycle 2 of combination dosing

Timeline

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

Oct 2013Aug 2014

First posted25 Sep 2013 (estimated)
Study startOct 2013
Primary completionAug 2014
Study completionAug 2014

Why it stopped: change in the development strategy

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Inoperable Locally Advanced or Metastatic Biliary Tract CancerStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01949870
Sponsor's protocol ID: D1532C00075
Status last verified: May 2016
First submitted: 10 Sep 2013
Last updated: 13 May 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-Label, Multi-Center Study to Assess the Safety and Tolerability of Selumetinib (AZD6244, ARRY-142886) in Combination With Cisplatin/Gemcitabine in Japanese Patients With Inoperable Locally Advanced or Metastatic Biliary Tract Cancer (BTC)
ClinicalTrials.gov ID: NCT01949870
Acronym / sponsor ID: D1532C00075
Conditions: Inoperable Locally Advanced or Metastatic Biliary Tract Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: change in the development strategy
Enrolment: 6 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Oct 2013
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 25 Sep 2013 (estimated)
Results: Posted 13 May 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Selumetinib	Other	Drug: Cisplatin, Drug: Gemcitabine, Drug: Selumetinib25mg/day, 50mg/day and 75mg/day

Who may qualify

Ages: 20 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Provision of written informed consent
Patients must be ≥ 20 years
Histological or cytological confirmation of locally advanced or metastatic BTC (intra- or extra-hepatic, gallbladder or ampullary carcinoma)
Patients who are eligible for treatment with standard dose of cisplatin/gemcitabine combination regimen
World Health Organisation (WHO) performance status (PS) 0-1

Key exclusion criteria (48 listed)

Treatment with any of the following:
With the exception of alopecia, any unresolved toxicities from prior therapy ≥Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, such as,
Any of the following cardiac criteria:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cisplatinday1 and day8 at each cycle	Drug	Selumetinib
Gemcitabineday1 and day8 at each cycle	Drug	Selumetinib
SelumetinibAlso: AZD624425mg/day, 50mg/day and 75mg/day	Drug	Selumetinib

Primary outcome

The Number of Dose-limiting Toxicities
Time frame: The first cycle with selumetinib until Day 1 of Cycle 2 of combination dosing
The number of dose-limiting toxicities in selumetinib in combination with cisplatin and gemcitabine

Results and safety

Results posted to the registry on 13 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Selumetinib+ Cisplatin + Gemcitabine	6	0

Primary outcome: The Number of Dose-limiting Toxicities

Time frame: The first cycle with selumetinib until Day 1 of Cycle 2 of combination dosing. Number. Unit: Participants

Measure	Selumetinib+ Cisplatin + Gemcitabine n = 3
Yes	0
No	3

Population analysed: Evaluable = completed at least 75% of planned daily doses of selumetinib at least 50% of planned dose of cisplatin/gemcitabine planned on Cycle 1 Day 8 (therefore, in total with Cycle 1 Day 1, at least 75 % of planned dose is given in Cycle 1) and has enough information to be assessed for the combination regimen dose escalation.

Adverse events

Time frame: AEs were collected throughout the study, from informed consent until the end of the followup period (28 days after last dose).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Selumetinib+ Cisplatin + Gemcitabine	1 of 4 (25%)	4 of 4 (100%)	Not reported

Limitations and caveats (from the sponsor): Dose escalation stopped after the first cohort due to changes in the drug development strategy. As such, a non-tolerated dose was not determined and the maximum tolerated dose could not be confirmed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cisplatin, Gemcitabine and Selumetinib in people with Inoperable Locally Advanced or Metastatic Biliary Tract Cancer, run by AstraZeneca at 2 sites in Japan.

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 8 inclusion and 48 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: stopped early, as of the sponsor's last update on 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Japan. 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?

Yes. Results are posted in the registry (first posted 13 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

The Number of Dose-limiting Toxicities (time frame: The first cycle with selumetinib until Day 1 of Cycle 2 of combination dosing). 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 NCT01949870.

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 13 May 2016.