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.

AstraZeneca

Status and phase: Terminated; Phase 1

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

Treatments: Drug: AZD1480 BID; Drug: AZD1480 Daily

Study type: Interventional

Funder types: Industry

Identifiers

NCT01219543

D1060C00004

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 4 patient groups

Part A

Experimental group

Description:

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

Treatment:

Drug: AZD1480 Daily

Part B

Experimental group

Description:

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

Treatment:

Drug: AZD1480 BID

Part C

Experimental group

Description:

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

Treatment:

Drug: AZD1480 BID

Expansion

Experimental group

Description:

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.

Treatment:

Drug: AZD1480 BID