A Phase 1 interventional study of AZD9150 in Advanced Adult Hepatocellular Carcinoma and Hepatocellular Carcinoma Metastatic, sponsored by AstraZeneca. Completed at 7 sites in 4 countries. Open to participants aged 18 Years to 130 Years. Per ClinicalTrials.gov, last updated 2017-03-06.
Sponsored by AstraZeneca · Phase 1, Interventional, and Treatment
This is a phase I/Ib open-label, multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD9150 in patients with advanced/metastatic hepatocellular carcinoma.
A Phase I/Ib, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9150 in Patients with Advanced/Metastatic Hepatocellular Carcinoma.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 58 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.
Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B).
Drug: AZD9150
Intravenous infusion over 3 hours.
Also known as: ISIS 481464
Number of Participants With Dose Limiting Toxicities During Cycle 1
Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22.
Time frame: DLT assessment window - Cycle 1 (22 days)
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data.
8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. From the multiple samples a timecourse is obtained of treatment conc in the plasma over time. From this curve the associated PK parameters e.g. Cmax are obtained. For n patients we obtain up to n parameters which can then be averaged.
Time frame: 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1.
Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response.
Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST). Overall tumour response: assessed by mRECIST for HCC overall visit response of CR (disappearance of baseline TLs and NTLs), PR (\>=30% decrease in sum of TLs), SD (neither PR nor PD), PD (sum TLs increased \>20%), or NE .
Time frame: Every 6 weeks, assessed up to 12 months.
Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data.
8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1.
Time frame: 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day 1 of Cycle 1.
The first patient entered the study on 03 May 2013, and the last patient last visit before the DCO was 31 December 2014. The DCO date was 05 January 2015.
| Milestone | AZD9150 1mg/kg | AZD9150 1.5 mg/kg | AZD9150 2mg/kg | AZD9150 2.5mg/kg | AZD9150 3mg/kg |
|---|---|---|---|---|---|
| Started | 6 | 6 | 7 | 5 | 15 |
| Completed | 6 | 6 | 7 | 5 | 15 |
| Not completed | 0 | 0 | 0 | 0 | 0 |
Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22.
| participants with DLT | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Number of Participants With Dose Limiting Toxicities During Cycle 1 | 0 | 1 | 1 | 2 | 3 |
8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. From the multiple samples a timecourse is obtained of treatment conc in the plasma over time. From this curve the associated PK parameters e.g. Cmax are obtained. For n patients we obtain up to n parameters which can then be averaged.
| ng/mL | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data. | 5833 ± 28.02 | 5575 ± 21.63 | 8984 ± 20.28 | 11560 ± 15.16 | 16110 ± 30.70 |
Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST). Overall tumour response: assessed by mRECIST for HCC overall visit response of CR (disappearance of baseline TLs and NTLs), PR (\>=30% decrease in sum of TLs), SD (neither PR nor PD), PD (sum TLs increased \>20%), or NE .
| participants with Partial Response | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response. | 0 | 0 | 1 | 0 | 0 |
8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1.
| h | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data. | 3.0 (1.5 to 3.0) | 3.4 (3.0 to 3.7) | 2.8 (1.5 to 3.5) | 3.0 (2.9 to 3.5) | 3.0 (1.3 to 3.0) |
Collected over AEs will be collected throughout the study, from informed consent until the end of the follow up period. The follow-up period is defined as 28 +/-7 days after study treatment is discontinued.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AZD9150 1mg/kg | — | 0/6 (0%) | 6/6 (100%) |
| 1.5 mg/kg | — | 0/6 (0%) | 6/6 (100%) |
| 2 mg/kg | — | 2/7 (28.6%) | 7/7 (100%) |
| 2.5 mg/kg | — | 2/5 (40%) | 5/5 (100%) |
| 3 mg/kg | — | 4/15 (26.7%) | 15/15 (100%) |
| Event | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Abdominal painGastrointestinal disorders | 0/6 | 0/6 | 0/7 | 1/5 | 0/15 |
| Hepatorenal failureHepatobiliary disorders | 0/6 | 0/6 | 0/7 | 1/5 | 0/15 |
| Aspartate aminotransferase increasedInvestigations | 0/6 | 0/6 | 1/7 | 1/5 | 0/15 |
| Liver abscessInfections and infestations | 0/6 | 0/6 | 1/7 | 0/5 | 0/15 |
| Peritoneal haemorrhageGastrointestinal disorders | 0/6 | 0/6 | 1/7 | 0/5 | 0/15 |
| Alanine amonitransferase increasedInvestigations | 0/6 | 0/6 | 1/7 | 0/5 | 0/15 |
| CellulitisInfections and infestations | 0/6 | 0/6 | 0/7 | 0/5 | 1/15 |
| AnaemiaBlood and lymphatic system disorders | 0/6 | 0/6 | 0/7 | 0/5 | 1/15 |
| Abdominal pain upperGastrointestinal disorders | 0/6 | 0/6 | 0/7 | 0/5 | 1/15 |
| Platelet count decreasedInvestigations | 0/6 | 0/6 | 0/7 | 0/5 | 1/15 |
| Event | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg |
|---|---|---|---|---|---|
| Aspartate aminotransferase increasedInvestigations | 3/6 | 4/6 | 5/7 | 3/5 | 9/15 |
| Platelet count decreasedInvestigations | 3/6 | 3/6 | 5/7 | 1/5 | 10/15 |
| Alanine aminotransferase increasedInvestigations | 2/6 | 3/6 | 4/7 | 3/5 | 9/15 |
| PruritusSkin and subcutaneous tissue disorders | 0/6 | 0/6 | 0/7 | 3/5 | 1/15 |
| DyspepsiaGastrointestinal disorders | 0/6 | 1/6 | 0/7 | 2/5 | 4/15 |
| ConstipationGastrointestinal disorders | 0/6 | 1/6 | 0/7 | 2/5 | 2/15 |
| Gamma-glutamylytransferase increasedInvestigations | 0/6 | 2/6 | 1/7 | 0/5 | 0/15 |
| CoughRespiratory, thoracic and mediastinal disorders | 2/6 | 0/6 | 0/7 | 1/5 | 2/15 |
| HypophosphataemiaMetabolism and nutrition disorders | 2/6 | 0/6 | 0/7 | 0/5 | 0/15 |
| HypertensionVascular disorders | 0/6 | 2/6 | 1/7 | 0/5 | 2/15 |
| Age, Continuous(years) | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg | Total |
|---|---|---|---|---|---|---|
| Mean | 59.3 ± 13.0 | 58.3 ± 12.9 | 64.1 ± 10.4 | 58.0 ± 11.0 | 57.5 ± 8.9 | 59.2 ± 10.4 |
| Gender(Participants) | AZD9150 1mg/kg | 1.5 mg/kg | 2 mg/kg | 2.5 mg/kg | 3 mg/kg | Total |
|---|---|---|---|---|---|---|
| Female | 0 | 1 | 2 | 2 | 0 | 5 |
| Male | 6 | 5 | 5 | 3 | 15 | 34 |
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