Advanced Solid Malignancies, Malignant Lymphoma
Conditions
Keywords
Advanced solid malignancies, Malignant lymphoma
Brief summary
The purpose of this study is to investigate the safety and tolerability of AZD 1208 up to a maximum tolerated dose (MTD) and define the dose(s) for further clinical evaluation when given daily to patients with advanced solid malignancies including malignant lymphoma
Detailed description
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD1208 in Patients with Advanced Solid Malignancies including Malignant Lymphoma
Interventions
DRUGAZD1208
Dose of AZD1208 will be escalated from 120mg to a maximum tolerated dose
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have signed this Written Informed Consent Form after a full explanation about the participation in this study * Patients aged 18 years or older Patients diagnosed with a solid malignant tumour or malignant lymphoma that is refractory to standard therapies or for which no standard therapies exist * Patients with good physical conditions (you can walk and can look after yourself) within the last 2 weeks. * Patients who have at least one lesion that can be accurately assessed
Exclusion criteria
* Patients who have recently received or are receiving prohibited medications or treatments * Patients who have any unresolved side effects of previous treatments * Patients who have spinal cord compression or brain metastases * Patients who have severe systemic diseases (e.g., uncontrolled hypertension, hepatitis B, hepatitis C and human immunodeficiency virus \[HIV\] infection) * Patients with significant abnormal ECG findings
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Measurements occur at screening (<=28 days before start of study treatment), every 6 weeks (+/-1 week) up to 12 weeks and then every 12 weeks (+/-1 week) until discontinuation of study treatment or withdrawal of consent, starting from Day 1 of Cycle 1 | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions (TL)s since baseline and any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm; Partial Response (PR), at least a 30% decrease in the sum of diameters of TLs; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD), at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm; Not Evaluable (NE), this is only relevant if any of the TLs were not assessed or not evaluable or had a lesion intervention at this visit, also note that if the sum of diameters meets the progressive disease criteria, progressive disease overrides not evaluable as a TL response. Best objective response is the best response a patient experiences over the randomised treatment period. |
Countries
Japan, United Kingdom
Participant flow
Pre-assignment details
43 patients were enrolled to the study, of which 35 recieved doses of AZD1208 between 120mg and 800mg. The other 8 patients did not receive AZD1208.
Participants by arm
| Arm | Count |
|---|---|
| AZD1208 120mg Once daily continuous dosing schedule. | 3 |
| AZD1208 240mg Once daily continuous dosing schedule. | 7 |
| AZD1208 360mg Once daily continuous dosing schedule. | 6 |
| AZD1208 540mg Once daily continuous dosing schedule. | 7 |
| AZD1208 700mg Once daily continuous dosing schedule. | 6 |
| AZD1208 800mg Once daily continuous dosing schedule. | 6 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 2 | 1 | 0 |
| Overall Study | Condition Under Investigation Worsened | 3 | 6 | 4 | 4 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | AZD1208 120mg | AZD1208 240mg | AZD1208 360mg | AZD1208 540mg | AZD1208 700mg | AZD1208 800mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.0 Years STANDARD_DEVIATION 9 | 59.4 Years STANDARD_DEVIATION 9.81 | 63.5 Years STANDARD_DEVIATION 14.38 | 62.3 Years STANDARD_DEVIATION 17.01 | 66.5 Years STANDARD_DEVIATION 12.85 | 60.8 Years STANDARD_DEVIATION 12.45 | 61.7 Years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 3 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 6 / 6 | 7 / 7 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 2 / 7 | 2 / 6 | 2 / 7 | 2 / 6 | 0 / 6 |
Outcome results
Primary
Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions (TL)s since baseline and any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm; Partial Response (PR), at least a 30% decrease in the sum of diameters of TLs; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD), at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm; Not Evaluable (NE), this is only relevant if any of the TLs were not assessed or not evaluable or had a lesion intervention at this visit, also note that if the sum of diameters meets the progressive disease criteria, progressive disease overrides not evaluable as a TL response. Best objective response is the best response a patient experiences over the randomised treatment period.
Time frame: Measurements occur at screening (<=28 days before start of study treatment), every 6 weeks (+/-1 week) up to 12 weeks and then every 12 weeks (+/-1 week) until discontinuation of study treatment or withdrawal of consent, starting from Day 1 of Cycle 1
Population: All patients who were evaluable for Response analysis set for RECIST criteria
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 2 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 1 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 0 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 0 Participants |
| AZD1208 120mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 5 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 240mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 2 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 1 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 0 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 3 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 0 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 1 Participants |
| AZD1208 360mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 0 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 0 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 3 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 3 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 1 Participants |
| AZD1208 540mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 0 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 2 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 1 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 2 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 700mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 1 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable(Incomplete postbaseline assessments) | 1 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (RECIST progression) | 3 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (unconfirmed CR or PR) | 0 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | SD >=6 weeks (SD) | 1 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PD (Death) | 0 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | PR | 0 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | Not evaluable (SD < 6 weeks) | 0 Participants |
| AZD1208 800mg | Best Objective Response Based on RECIST Criteria (Evaluable for Response Analysis Set for RECIST Criteria) | CR | 0 Participants |