Tumors With Aberrations in ALK or ROS1 Clinical Trial
— SIGNATUREOfficial 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
| Verified date | March 2021 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 47 |
| Est. completion date | December 13, 2017 |
| Est. primary completion date | December 13, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Andrew and Patel Associates | Camp Hill | Pennsylvania |
| United States | Physicians Clinic of Iowa | Cedar Rapids | Iowa |
| United States | Northwestern University Northwestern (6) | Chicago | Illinois |
| United States | Columbus Hematology and Oncology PA Columbus Hem and Onc (2) | Columbus | Ohio |
| United States | Sarah Cannon Research Institute | Denver | Colorado |
| United States | Duke University Medical Center Seeley G. Mudd Bldg. | Durham | North Carolina |
| United States | Sanford Hematology Oncology | Fargo | North Dakota |
| United States | Florida Cancer Specialists Florida Cancer Specialists (31 | Fort Myers | Florida |
| United States | Rocky Mountain Cancer Centers Dept of Rocky Mountain (2) | Greenwood Village | Colorado |
| United States | MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3) | Houston | Texas |
| United States | Oncology Consultants Oncology Group | Houston | Texas |
| United States | Comprehensive Cancer Centers of Nevada CCC of Nevada (1) | Las Vegas | Nevada |
| United States | Southeast Nebraska Oncology | Lincoln | Nebraska |
| United States | Aurora Research Institute | Milwaukee | Wisconsin |
| United States | Rhode Island Hospital Rhode Island Hosp. (2) | Providence | Rhode Island |
| United States | Utah Cancer Specialists Utah Cancer Specialists | Salt Lake City | Utah |
| United States | St Joseph Heritage Healthcare St. Joseph Heritage | Santa Rosa | California |
| United States | Swedish Cancer Institute Swedish Cancer Institute | Seattle | Washington |
| United States | Holy Cross Hospital Holy Cross (2) | Silver Spring | Maryland |
| United States | Sanford University of South Dakota Medical Center Sanford Clinical Research | Sioux Falls | South Dakota |
| United States | Wake Forest Baptist Health Health Sciences | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks | Solid tumors were assessed using RECIST 1.1 criteria and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least 30% decrease in sum of diameters of target lesions from baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of measured target lesions from smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was considered PD. Overall response rate (ORR) = (CR + PR). Clinical benefit rate = (CR + PR + SD) | Baseline up to approximately 16 weeks | |
| Primary | Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks | For patients with solid tumors the assessment criteria was RECIST 1.1 and included responses of complete response (CR) or partial response (PR) or stable disease (SD). For hematologic tumors, other hematological response criteria applied. CR=disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR=at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Progressive disease (PD)=at least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline (sum must also demonstrate an absolute increase of at least 5mm). One or more new lesions was also considered progression. | Baseline up to approximately 16 weeks | |
| Secondary | Progression-Free Survival (PFS) | Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment. | Baseline up to approximately 27 months | |
| Secondary | Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates | Progression-free survival (PFS) was the time from the date of start of study drug to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a patient has not had an event, progression-free survival was censored at the date of last adequate tumor assessment. | Basleline up to approximately 27 months | |
| Secondary | Overall Survival (OS) - Number of Participant Deaths | Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause | Baseline up to approximately 27 months | |
| Secondary | Duration of Response (DOR) | Duration of response (DOR) is defined as time from the first documented response (CR or PR) to the date first documented disease progression or relapse or death due to any cause | baseline up to approximately 30 months |