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

NCT01949870 | Terminated Phase 1 Results

• 1 other identifier: D1532C00075
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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

Outcome Measures

Primary Outcomes (1)

• The Number of Dose-limiting Toxicities

  The number of dose-limiting toxicities in selumetinib in combination with cisplatin and gemcitabine

  The first cycle with selumetinib until Day 1 of Cycle 2 of combination dosing

Study Arms (1)

Selumetinib

OTHER

25mg/day, 50mg/day and 75mg/day

Drug: Cisplatin; Drug: Gemcitabine; Drug: Selumetinib

Interventions

Cisplatin DRUG

day1 and day8 at each cycle

Selumetinib

Gemcitabine DRUG

day1 and day8 at each cycle

Selumetinib

Selumetinib DRUG

25mg/day, 50mg/day and 75mg/day

Also known as: AZD6244

Selumetinib

Eligibility Criteria

• Age: 20 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ii) 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

AZD6244 PhI Japanese Gem/

Kashiwa Shi, Chiba, Japan

Location

AZD6244 PhI Japanese Gem/

Chuo Ku, Tokyo, Japan

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Cisplatin; Gemcitabine; AZD 6244

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr Gabriella Mariani
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+44 7818 523 899

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 25, 2013
• Study Start: October 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: May 13, 2016
• Results First Posted: May 13, 2016

Record last verified: 2016-05

Locations

JP (2)