The primary objective of the study is to determine the efficacy of AP26113, as evidenced by objective response rate, in patients with ALK positive locally advanced or metastatic NSCLC whose disease has progressed on therapy with crizotinib.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Confirmed Objective Response Rate (ORR), as assessed by the investigator, per
RECIST v1.1
Secondary outcome
Secondary Endpoints:
1. Confirmed ORR, as assessed by a central independent review committee (IRC),
per RECIST v1.1
2. CNS response (ORR and PFS, per RECIST v1.1, in patients who have active
brain metastases)
3. Time to response
4. Duration of response
5. Time on treatment
6. Disease control rate (the percentage of patients with best response of
complete response [CR], PR, or SD), per RECIST v1.1
7. Progression Free Survival (PFS)
8. Overall Survival (OS)
9. Safety and tolerability
10. Steady-state plasma level of AP26113 for use in population PK modeling
11. Patient-reported symptoms of lung cancer and HRQoL scores, assessed with
the EORTC QLQ-C30 (v3.0)
Background summary
AP26113 is a novel, synthetic, orally-active tyrosine kinase inhibitor (TKI)
discovered and developed at ARIAD Pharmaceuticals, Inc. (ARIAD, the sponsor).
A primary target of AP26113 is anaplastic lymphoma kinase (ALK). Activating
gene rearrangements in ALK-positive (ALK+) tumors have been identified as
driver mutations in patients with non-small cell lung cancer (NSCLC) and other
cancers.
Study objective
The primary objective of the study is to determine the efficacy of AP26113, as
evidenced by objective response rate, in patients with ALK positive locally
advanced or metastatic NSCLC whose disease has progressed on therapy with
crizotinib.
Study design
Phase 2, open-label, randomized, multicenter, international study.
Intervention
Patients will be randomized 1:1 to receive AP26113 in one of two different
dosing regimens.
Arm A: AP26113 will be administered at a dose of 90 mg QD, continuously.
Arm B: AP26113 will be administered at a dose of 90 mg QD for 7 days, then 180
mg QD, continuously.
A cycle of therapy will comprise 28 days of treatment, regardless of dose
Study burden and risks
Throughout the study, the Study Doctor will monitor the patients condition by
examining and performing various tests that are described below. Most of the
tests are similar to those performed as part of the standard care of patients
with this type of cancer. Some of the tests are done to find out as early as
possible if the patient is experiencing any side effects. The tests that are
done extra for this study are: extra blood samples; a possible tumor biopsy
before study start (if no recent sample available) and an extra possible tumor
biopsy during the study (if the patient consents to this study); ECG(s).
Landsdowne Street 40
Cambridge, MA MA 02139
US
Landsdowne Street 40
Cambridge, MA MA 02139
US
Listed location countries
Age
Inclusion criteria
All patients must meet all the following eligibility criteria for study entry:
1. Have histologically or cytologically confirmed locally advanced or
metastatic NSCLC that is ALK+.
2. Must meet one of the following two criteria:
a. Have documented ALK rearrangement by a positive result from the Vysis® ALK
Break-Apart fluorescence in situ hybridization (FISH) Probe Kit; or
b. Have documented ALK positivity by a different test and tissue available for
the Vysis® FISH test. Tissue should
be derived preferably from abiopsy taken after progression with crizotinib. If
such a sample is not available, testing
may be performed with archived tumor tissue.
3. Had progressive disease while on crizotinib, as assessed by the investigator
or treating physician.
4. Received crizotinib as the last therapy, within 30 days of the first dose of
AP26113. This criterion may be met by
reintroduction of crizotinib after intervening therapy. If crizotinib was
reintroduced, documented progression on the
most recent regimen of crizotinib must have occurred.
8. Are a male or female patient >=18 years old.
Exclusion criteria
Patients meeting any of the criteria below are ineligible for the study:
1. Received any prior ALK-targeted TKI other than crizotinib.
2. Received crizotinib within 3 days of the first dose of AP26113 (Day 1,
Cycle1).
3. Received cytotoxic chemotherapy, investigational agents, or radiation within
14 days, except SRS or
stereotactic body radiosurgery.
4. Received monoclonal antibodies or had major surgery within 30 days of the
first dose of AP26113 (Day 1, Cycle 1).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 111 |
| EudraCT | EUCTR2013-002134-21-NL |
| CCMO | NL46797.042.14 |