Neoplasms
Conditions
Brief summary
This open-label dose escalation phase I trial, 1280.15, is with the first administration of BI 836845 in Japanese patients with various types of advanced solid tumours. The rationale behind this study is to identify the maximum tolerated dose (MTD) of BI 836845 in Japanese patients with advanced solid tumours as weekly intravenous administration.
Interventions
DRUG750 milligram Xentuzumab
750 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.
DRUG1000 milligram Xentuzumab
1000 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.
DRUG1400 milligram Xentuzumab
1400 milligram Xentuzumab given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities.
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients who meet all of the following inclusion criteria by the judgment of investigator are eligible to receive the study treatment: 1. Patients with cytologically or histologically confirmed solid tumours that are refractory to standard therapy, for whom no standard therapy of proven efficacy exists, or who are not amenable to establish treatment options 2. Age \>=20 years old 3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 4. Written informed consent that is consistent with Good Clinical Practice (GCP) guidelines
Exclusion criteria
Patients who apply any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Xentuzumab in Japanese Patients With Advanced Solid Tumours, as Identified by the Number of Patients With Dose-limiting Toxicities (DLTs) | During the first cycle of treatment, up to 21 days of treatment. | MTD of xentuzumab in Japanese patients with advanced solid tumours, as identified by the number of patients with DLTs. The MTD of xentuzumab was defined as the highest dose tested with DLT occurring in not more than 1 out of 6 evaluable patients. DLTs were defined as: Haematological toxicities: Common Terminology Criteria for Adverse Events (CTCAE) grade (g) 4 neutropenia ≥7 days (d), select cases of Febrile neutropenia, Infections or CTCAE g4 thrombocytopenia or CTCAE g3 thrombocytopenia. Non-haematological toxicities: CTCAE grade 3 or 4 non-haematologic toxicity, with exceptions CTCAE grade≥2 infusion reaction or nausea and/or vomiting with exceptions CTCAE grade ≥3 skin toxicity, hyperglycaemia, any electrolyte adverse events (AE), fatigue or asthenia with exceptions No recovery from a non-DLT CTCAE g≥3 toxicity to g≤1 within 14 d of administered dose Other drug-related AEs (CTCAE g2), might qualify as a DLT, which will be determined on a case by case bases. |
Countries
Japan
Participant flow
Recruitment details
This was an open-label study, with a dose escalation cohort according to a 3+3 design followed by an expansion cohort.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 750 Milligram Xentuzumab (BI 836845) 750 milligram Xentuzumab (BI 836845) given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities. | 6 |
| 1000 Milligram Xentuzumab (BI 836845) 1000 milligram Xentuzumab (BI 836845) given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities. | 9 |
| 1400 Milligram Xentuzumab (BI 836845) 1400 milligram Xentuzumab (BI 836845) given weekly (days 1, 8, and 15) as an intravenous infusion over 1 hour. Patients stayed on treatment in 21-day cycles until disease progression or undue toxicities. | 6 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Progressive disease | 3 | 6 | 6 |
| Overall Study | quality issue with the administered drug | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | 750 Milligram Xentuzumab (BI 836845) | 1000 Milligram Xentuzumab (BI 836845) | 1400 Milligram Xentuzumab (BI 836845) | Total |
|---|---|---|---|---|
| Age, Continuous | 60.33 years STANDARD_DEVIATION 10.82 | 52.00 years STANDARD_DEVIATION 16.58 | 64.67 years STANDARD_DEVIATION 9.16 | 58.00 years STANDARD_DEVIATION 21.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 9 Participants | 6 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 9 Participants | 6 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 3 / 6 | 9 / 9 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 3 / 9 | 0 / 6 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Xentuzumab in Japanese Patients With Advanced Solid Tumours, as Identified by the Number of Patients With Dose-limiting Toxicities (DLTs)
MTD of xentuzumab in Japanese patients with advanced solid tumours, as identified by the number of patients with DLTs. The MTD of xentuzumab was defined as the highest dose tested with DLT occurring in not more than 1 out of 6 evaluable patients. DLTs were defined as: Haematological toxicities: Common Terminology Criteria for Adverse Events (CTCAE) grade (g) 4 neutropenia ≥7 days (d), select cases of Febrile neutropenia, Infections or CTCAE g4 thrombocytopenia or CTCAE g3 thrombocytopenia. Non-haematological toxicities: CTCAE grade 3 or 4 non-haematologic toxicity, with exceptions CTCAE grade≥2 infusion reaction or nausea and/or vomiting with exceptions CTCAE grade ≥3 skin toxicity, hyperglycaemia, any electrolyte adverse events (AE), fatigue or asthenia with exceptions No recovery from a non-DLT CTCAE g≥3 toxicity to g≤1 within 14 d of administered dose Other drug-related AEs (CTCAE g2), might qualify as a DLT, which will be determined on a case by case bases.
Time frame: During the first cycle of treatment, up to 21 days of treatment.
Population: The Maximum tolerated dose (MTD) set was defined as the set of patients that were fully evaluable for the MTD in the first treatment cycle.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xentuzumab (BI 836845) | Maximum Tolerated Dose (MTD) of Xentuzumab in Japanese Patients With Advanced Solid Tumours, as Identified by the Number of Patients With Dose-limiting Toxicities (DLTs) | NA Milligram |