A Phase I Study of AZD1480 in Patients With Advanced Solid Malignancies and Advanced Hepatocellular Carcinoma in the Escalation Phase,Non-Small Cell Lung Cancer(NSCLC) and Non-smokers With Lung Metastasis and Gastric Cancer and Solid Tumour in the Expansion Phase.

NCT01219543 | Terminated Phase 1

• 1 other identifier: D1060C00004
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This is Phase I, open-label and dose escalation study to evaluate the safety and tolerability of AZD1480(JAK2 inhibitor) in Asian patients with advanced solid tumors (Part A and C) and in patients with advanced HCC (Part B) in the escalation phase, EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer in the expansion phase and to evaluate daily and BID dosing.

Conditions

Solid Tumour; Advanced Solid Malignancies; Child-Pugh A to B7 Advanced Hepatocellular Carcinoma; EGFR and/or ROS Mutant NSCLC; Lung Metastasis Carcinoma; Gastric Cancer

Keywords

Advanced solid malignancies; Child-Pugh A to B7 advanced hepatocellular carcinoma; EGFR and/or ROS mutant NSCLC; Non-smokers with lung metastasis; Gastric cancer; Solid tumour; AZD1480; JAK1/JAK2 kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• To investigate the safety and tolerability of AZD1480

  Safety and tolerability monitoring will proceed for whole study period. Screening, Cycle1Day1, Cycle1Day5 (only for Part B), Cycle1Day8, Cycle1Day15, Cycle2Day1, Cycle2Day8 and Day1 of further Cycles, IP discontinued visit and 30-days follow up

Secondary Outcomes (2)

• To evaluate the pharmacokinetics (PK) of AZD1480 following single dose and multiple doses

  Part A and Expansion - 12 times during Cycle 1, 11 times during Cycle 2. Part B and C - 11 times during Cycle 1, 10 times during Cycle 2. *1 additional PK sample in Cycle 1 will be collect for optional biopsy sample collected patients.

• To obtain a preliminary assessment of the anti-tumour activity of AZD1480

  Tumour response assessment by RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1 every 6 weeks

Study Arms (4)

Part A

EXPERIMENTAL

Daily dosing of AZD1480 to the patients with solid tumours excluding HCC

Drug: AZD1480 Daily

Part B

EXPERIMENTAL

BID dosing of AZD1480 to the patients with advanced HCC (Child-Pugh A to B7)

Drug: AZD1480 BID

Part C

EXPERIMENTAL

BID dosing of AZD1480 to the patients with solid tumours excluding HCC

Drug: AZD1480 BID

Expansion

EXPERIMENTAL

BID dosing of AZD1480 to the patients with EGFR or ROS mutant NSCLC and non-smokers with lung metastasis and gastric cancer and solid tumour with biopsy available.

Drug: AZD1480 BID

Interventions

AZD1480 Daily DRUG

Oral Dose, Capsule, Daily Dosing

Part A

AZD1480 BID DRUG

Oral Dose, Capsule, BID Dosing

Expansion; Part B; Part C

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18 years or older
• For Part A and C: Histological or cytological confirmation of a solid malignant tumour refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma \& HCC are excluded.
• For Expansion : Histological or cytological confirmation of
• Expansion 1: EGFR and/or ROS mutant NSCLC or Non-smokers with lung metastasis
• Expansion 2: Gastric cancer or solid tumour with biopsy available (consenting paired biopsies)refractory to standard therapies or for which no standard therapies exist. Patients with lymphoma \& HCC are excluded.
• For Part B : Advanced or metastatic HCC, unresectable and incurable with ablative therapy or TACE, with no standard therapy available.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks
• For Part B : Child-Pugh liver function status classified as A to B7

You may not qualify if:

• For any other chemotherapy, immunotherapy or anticancer agents, within 5 half lives or 3 weeks must have elapsed from treatment to of the first dose of investigational product, whichever is shorter.
• With the exception of alopecia, any unresolved toxicities from prior therapy ≥ Grade 2 of CTCAE V4.02 at the time of starting study (except LFTs for HCC patients, which may be Grade 2 at the time of starting the study)
• Any of the following conditions:Interferon treatment for HBV and HCV Prior Liver Transplantation
• Inadequate bone marrow reserve or organ function as demonstrated by laboratory values
• Evidence of established interstitial lung disease(ILD) on baseline high resolution computerized tomography(HRCT)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Becker Hewes, MD

  AstraZeneca

  STUDY DIRECTOR

• Kang Yoon-Koo, MD, PhD

  Asian Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 11, 2010
• First Posted: October 13, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 8, 2013

Record last verified: 2013-01

Locations

KR (1)