Advanced Solid Tumors
Conditions
Keywords
c-Met overexpression, MET amplification, Neoplasms, h224G11
Brief summary
This is a Phase 1/1b open-label study evaluating the safety, pharmacokinetics (PK), and preliminary efficacy of ABT-700 in subjects with advanced solid tumors that may have MET amplification or c-Met overexpression. ABT-700, previously known as h224G11 in publications, is an anti-c-Met antibody. The early clinical development plan for ABT-700 is based on the activity demonstrated in preclinical models. Up to 124 subjects will be enrolled.
Interventions
DRUGABT-700
ABT-700 will be administered by intravenous infusion at escalating dose levels on day 1 in 21-day dosing cycles. Additional subjects will be enrolled in an dose expansion cohort that will further evaluate ABT-700.
DRUGdocetaxel
Docetaxel will be administered by intravenous infusion on Day 1 in 21-day dosing cycles.
DRUGFOLFIRI
5-fluorouracil, Folinic acid and Irinotecan will be administered by intravenous infusion on Day 1 and 15 in 28-day dosing cycles.
DRUGcetuximab
Cetuximab will be administered by intravenous infusion weekly.
DRUGerlotinib
Erlotinib will be taken orally daily.
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Subject with advanced solid tumors; Dose-expansion: evidence for MET gene amplification. * Subject must have disease: a) that is not amenable to surgical resection, or b) that has progressed or recurred despite standard therapy, or c) that has failed to respond to standard therapy, or d) for which no effective therapy exists. * Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage. * Subjects enrolled on the combination therapy phase must satisfy the above inclusion criteria and also the following: Subjects must have inoperable, locally advanced or metastatic cancer and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib in combination with ABT-700.
Exclusion criteria
* Subject has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within a period of 21 days, or herbal therapy within 7 days prior to the first dose of ABT-700. * Subjects with uncontrolled metastases of the central nervous system. Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease after definitive therapy and have not used steroids for at least 1 month prior to first dose of ABT-700. * Subject has unresolved adverse events \> Grade 1 from prior anticancer therapy except for alopecia or anemia. * Subject has had major surgery within 21 days prior to the first dose of ABT-700. * Subjects enrolled on the combination therapy phase must not meet the above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety and tolerability of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib | First cycle of treatment through 60 day follow-up visit | Evaluation of vital signs, clinical lab testing, physical exams and adverse event monitoring |
| To Evaluate the pharmacokinetics of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib | At each cycle of treatment through 60 days after last dose. | Pharmacokinetic profile of ABT-700 analyzed from blood samples |
| To determine the recommended Phase 2 dose for ABT-700 | First cycle of treatment through 60 day follow-up visit | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the preliminary efficacy of ABT-700 when administered as monotherapy and in combination with docetaxel or 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or erlotinib | Screening through 60 day follow-up visit | Objective response rate (complete and partial response), progression-free survival and duration of response |
Outcome results
None listed