Tumors
Conditions
Keywords
Advanced Solid Tumours, phase II, Hypertension, RECENTIN
Brief summary
The purpose of this study is to determine whether doses of 30 mg and 45 mg AZD2171 can be well tolerated without significant drug withdrawal when accompanied by a suitable hypertension management strategy or dose reduction.
Interventions
DRUGAZD2171
30 mg & 45 mg oral tablet
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmation of advanced solid tumour, which is refractory to standard therapies or for which no standard therapy exists and for which there is a rationale for the therapeutic use of a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor.
Exclusion criteria
* Prior treatment with a VEGF inhibitor * Poorly controlled hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171 | 12 week treatment period | — |
| Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171 | 12 week treatment period | Total actual dose received during the first 12 weeks prior to progression divided by the planned dose (planned dose: initial allocated dose multiplied by the number of days on study during the first 12 weeks prior to progression) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171 | First 6 weeks of 12 week treatment period | — |
| Objective Response Rate | 12 week treatment period | Number of patients with complete or partial response (CR/PR), based on RECIST |
| Best Percentage Change in Tumour Size | Randomisation until end of treatment period | Maximum percentage reduction or minimum percentage increase in tumour size where size is the sum of the longest diameters of the target lesions. Based on the baseline scaled ratio: ratio of the post-randomisation visit tumour size divided by the baseline tumour size. |
Countries
Germany, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD2171 30 mg Anti HT AZD2171 30 mg AntiHT prophylaxis | 30 |
| AZD2171 30 mg No Anti HT AZD2171 30 mg No AntiHT prophylaxis | 32 |
| AZD2171 45 mg Anti HT AZD2171 45 mg AntiHT prophylaxis | 30 |
| AZD2171 45 mg No Anti HT AZD2171 45 mg No AntiHT prophylaxis | 34 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 6 | 4 |
| Overall Study | Cond. under inv. worsened | 9 | 5 | 3 | 4 |
| Overall Study | Development study specific disc. crit. | 1 | 0 | 1 | 0 |
| Overall Study | Not treated | 3 | 0 | 2 | 2 |
| Overall Study | Other | 2 | 2 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | AZD2171 30 mg Anti HT | AZD2171 30 mg No Anti HT | AZD2171 45 mg Anti HT | AZD2171 45 mg No Anti HT | Total |
|---|---|---|---|---|---|
| Age Continuous Age | 58.1 Years STANDARD_DEVIATION 9.3 | 52.7 Years STANDARD_DEVIATION 12.9 | 56.4 Years STANDARD_DEVIATION 11 | 53.5 Years STANDARD_DEVIATION 11.7 | 55.175 Years STANDARD_DEVIATION 11.225 |
| Sex: Female, Male Female | 12 Participants | 16 Participants | 13 Participants | 25 Participants | 66 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 17 Participants | 9 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 28 | 34 / 31 | 27 / 26 | 26 / 34 |
| serious Total, serious adverse events | 19 / 28 | 20 / 31 | 10 / 26 | 10 / 34 |
Outcome results
Primary
Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171
Time frame: 12 week treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 30 mg Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171 | 12 Participants |
| AZD2171 30 mg No Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171 | 19 Participants |
| AZD2171 45 mg Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171 | 20 Participants |
| AZD2171 45 mg No Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 12 Weeks of First Dose of AZD2171 | 24 Participants |
Primary
Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171
Total actual dose received during the first 12 weeks prior to progression divided by the planned dose (planned dose: initial allocated dose multiplied by the number of days on study during the first 12 weeks prior to progression)
Time frame: 12 week treatment period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD2171 30 mg Anti HT | Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171 | 0.89 Poportion of Planned Dose |
| AZD2171 30 mg No Anti HT | Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171 | 0.88 Poportion of Planned Dose |
| AZD2171 45 mg Anti HT | Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171 | 0.74 Poportion of Planned Dose |
| AZD2171 45 mg No Anti HT | Proportion of Planned Dose Received During First 12 Weeks of Therapy With AZD2171 | 0.79 Poportion of Planned Dose |
Secondary
Best Percentage Change in Tumour Size
Maximum percentage reduction or minimum percentage increase in tumour size where size is the sum of the longest diameters of the target lesions. Based on the baseline scaled ratio: ratio of the post-randomisation visit tumour size divided by the baseline tumour size.
Time frame: Randomisation until end of treatment period
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD2171 30 mg Anti HT | Best Percentage Change in Tumour Size | -1.12 percentage of tumor size |
| AZD2171 30 mg No Anti HT | Best Percentage Change in Tumour Size | -10.81 percentage of tumor size |
| AZD2171 45 mg Anti HT | Best Percentage Change in Tumour Size | -11.78 percentage of tumor size |
| AZD2171 45 mg No Anti HT | Best Percentage Change in Tumour Size | -13.13 percentage of tumor size |
Secondary
Objective Response Rate
Number of patients with complete or partial response (CR/PR), based on RECIST
Time frame: 12 week treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 30 mg Anti HT | Objective Response Rate | 1 Participants |
| AZD2171 30 mg No Anti HT | Objective Response Rate | 3 Participants |
| AZD2171 45 mg Anti HT | Objective Response Rate | 2 Participants |
| AZD2171 45 mg No Anti HT | Objective Response Rate | 3 Participants |
Secondary
Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171
Time frame: First 6 weeks of 12 week treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AZD2171 30 mg Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171 | 9 Participants |
| AZD2171 30 mg No Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171 | 9 Participants |
| AZD2171 45 mg Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171 | 16 Participants |
| AZD2171 45 mg No Anti HT | Proportion of Patients Requiring Temporary (>1 Day) or Permanent Withdrawal of AZD2171 Prior to Progression and Within 6 Weeks of First Dose of AZD2171 | 19 Participants |