Clinical trial NCT02186821: Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)
Official title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module - 7 Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Tumors With Aberrations in ALK or ROS1
Keywords: hematological malignancy
solid tumor malignancy
mutation
translocation
rearrangement
amplification
ALK
ROS1
NSCLC
B-cell lymphoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-07-10
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this signal seeking study was to determine whether treatment with ceritinib demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

Detailed description: This was an open label study to determine the efficacy and safety of treatment with ceritinib in patients with a diagnosis of solid tumors or hematological malignancies that had been pre-identified (prior to study consent) to have ALK or ROS1 positive mutations, translocations, rearrangements or amplifications and whose disease had progressed on or after standard treatment. The study consisted of a treatment phase where all patients received ceritinib capsules for a total dose of 750 mg daily for up to 8 cycles of 28 days. Disease assessments for clinical benefit were performed every 8 weeks until disease progression or end of treatment. Following discontinuation of treatment for any reason, patients were followed for safety for 30 days. Survival information was collected every 3 months until 2 years after the last patient had enrolled into the study. Study was amended to allow for discontinuation of survival period if primary endpoint was not met.

Study was terminated due to low enrollment.

Eligibility criteria: Inclusion Criteria:

* Patient had a confirmed diagnosis of a select solid tumor (except ALK+ NSCLC) or hematological malignancy and was in need of treatment because of radiologic progression or relapse.
* Patient must have been pre-identified as having a tumor with an ALK or ROS1 positive mutation, translocation, rearrangement or amplification. The qualifying alteration must have been assessed and reported by a CLIA-certified laboratory. ALK positivity as assessed by IHC or FISH were allowed.
* Patient must have received at least one prior treatment for recurrent, metastatic and/or locally advanced disease and for whom no standard therapy options were anticipated to result in a durable remission.
* Patient had progressive and measurable disease as per RECIST 1.1 or other appropriate hematological guidelines.
* Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

Exclusion Criteria:

* Patient had received prior treatment with ceritinib.
* Patients with symptomatic CNS metastases who were neurologically unstable or required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
* Patient had received chemotherapy or anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, monoclonal antibodies or mitomycin-C) prior to starting study drug.

Primary outcomes:
measure: Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks
timeFrame: Baseline up to approximately 16 weeks
measure: Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks
timeFrame: Baseline up to approximately 16 weeks
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to approximately 27 months
measure: Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates
timeFrame: Basleline up to approximately 27 months
measure: Overall Survival (OS) - Number of Participant Deaths
timeFrame: Baseline up to approximately 27 months
measure: Duration of Response (DOR)
timeFrame: baseline up to approximately 30 months
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare St. Joseph Heritage
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Florida Cancer Specialists (31
state: Florida
city: Chicago
country: United States
facility: Northwestern University Northwestern (6)
state: Illinois
city: Cedar Rapids
country: United States
facility: Physicians Clinic of Iowa
state: Iowa
city: Silver Spring
country: United States
facility: Holy Cross Hospital Holy Cross (2)
state: Maryland
city: Lincoln
country: United States
facility: Southeast Nebraska Oncology
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
state: Nevada
city: Durham
country: United States
facility: Duke University Medical Center Seeley G. Mudd Bldg.
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Hematology Oncology
state: North Dakota
city: Columbus
country: United States
facility: Columbus Hematology and Oncology PA Columbus Hem and Onc (2)
state: Ohio
city: Camp Hill
country: United States
facility: Andrew and Patel Associates
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Rhode Island Hosp. (2)
state: Rhode Island
city: Sioux Falls
country: United States
facility: Sanford University of South Dakota Medical Center Sanford Clinical Research
state: South Dakota
city: Houston
country: United States
facility: Oncology Consultants Oncology Group
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Utah Cancer Specialists
state: Utah
city: Seattle
country: United States
facility: Swedish Cancer Institute Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute
state: Wisconsin
Study officials:
References: