Tumors With Aberrations in ALK or ROS1Phase 2SIGNATURENCT02186821

Ceritinib (LDK378) for Patients Whose Tumors Have Aberrations in ALK or ROS1 (SIGNATURE)

A Phase 2 study testing Ceritinib in people with Tumors With Aberrations in ALK or ROS1, run by Novartis Pharmaceuticals at 21 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Tumors With Aberrations in ALK or ROS1
What is being tested?: Ceritinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 47 participants
Where: 21 sitesUnited States
Study dates: 17 Sep 2014to 13 Dec 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

21 sites in 1 country.

City, postcode or hospital

21 sites in 1 country

United States21 sites

Andrew and Patel Associates
Camp Hill, Pennsylvania, 17011
Physicians Clinic of Iowa
Cedar Rapids, Iowa, 52403
Northwestern University Northwestern (6)
Chicago, Illinois, 60611
Columbus Hematology and Oncology PA Columbus Hem and Onc (2)
Columbus, Ohio, 39705
Sarah Cannon Research Institute
Denver, Colorado, 80218
Duke University Medical Center Seeley G. Mudd Bldg.
Durham, North Carolina, 27710
Sanford Hematology Oncology
Fargo, North Dakota, 58122
Florida Cancer Specialists Florida Cancer Specialists (31
Fort Myers, Florida, 33901
Rocky Mountain Cancer Centers Dept of Rocky Mountain (2)
Greenwood Village, Colorado
Oncology Consultants Oncology Group
Houston, Texas, 77024
MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
Houston, Texas, 77030
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
Las Vegas, Nevada, 89109
Southeast Nebraska Oncology
Lincoln, Nebraska, 68510
Aurora Research Institute
Milwaukee, Wisconsin, 53226
Rhode Island Hospital Rhode Island Hosp. (2)
Providence, Rhode Island, 02903
Utah Cancer Specialists Utah Cancer Specialists
Salt Lake City, Utah, 84106
St Joseph Heritage Healthcare St. Joseph Heritage
Santa Rosa, California, 94503
Swedish Cancer Institute Swedish Cancer Institute
Seattle, Washington, 98104
Holy Cross Hospital Holy Cross (2)
Silver Spring, Maryland, 20910
Sanford University of South Dakota Medical Center Sanford Clinical Research
Sioux Falls, South Dakota, 57104
Wake Forest Baptist Health Health Sciences
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

Read the 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.

Conditions: Tumors With Aberrations in ALK or ROS1
Being tested: Ceritinib
Keywords: hematological malignancy, solid tumor malignancy, mutation, translocation, rearrangement, amplification, ALK, ROS1, NSCLC, B-cell lymphoma
Medical subject headings: Hematologic Neoplasms, Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CeritinibDrug
Also called LDK378
Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally,once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days. There were no breaks between dosing cycles.

Study groups in NCT02186821
Study group	Role	What they receive
Ceritinib 750 mg	Experimental	Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles. Receives: Drug: Ceritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: Baseline up to approximately 16 weeks
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.
Measured: Baseline up to approximately 16 weeks

Secondary outcomes (4)

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.
Measured: Baseline up to approximately 27 months
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.
Measured: Basleline up to approximately 27 months
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
Measured: Baseline up to approximately 27 months
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
Measured: baseline up to approximately 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Sep 201413 Dec 2017

First posted10 Jul 2014 (estimated)
Study start17 Sep 2014
Primary completion13 Dec 2017
Study completion13 Dec 2017

Why it stopped: Study was terminated due to low enrollment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Tumors With Aberrations in ALK or ROS1Studies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 47 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02186821
Sponsor's protocol ID: CLDK378AUS23
Acronym: SIGNATURE
Status last verified: Mar 2021
First submitted: 3 Jul 2014
Last updated: 8 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 8 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02186821
Acronym / sponsor ID: SIGNATURE / CLDK378AUS23
Conditions: Tumors With Aberrations in ALK or ROS1
Keywords: hematological malignancy, solid tumor malignancy, mutation, translocation, rearrangement, amplification, ALK, ROS1
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study was terminated due to low enrollment
Enrolment: 47 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 17 Sep 2014 (actual)
Primary completion: 13 Dec 2017 (actual)
Study completion: 13 Dec 2017 (actual)
First posted: 10 Jul 2014 (estimated)
Results: Posted 8 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study was terminated due to low enrollment.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Ceritinib 750 mg	Experimental	Drug: CeritinibCeritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally, once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days with no breaks between dosing cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CeritinibAlso: LDK378Ceritinib was dosed on a flat scale of 750 mg (e.g., 5 x 150 mg capsules) orally,once daily, on a continuous dosing cycle. A complete treatment cycle was defined as 28 days. There were no breaks between dosing cycles.	Drug	Ceritinib 750 mg

Primary outcome

Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks
Time frame: Baseline up to 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)
Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks
Time frame: Baseline up to 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.

4 secondary outcomes

Progression-Free Survival (PFS)
Time frame: Baseline up to approximately 27 months
Percentage of Participants With Progression-Free Survival (PFS) - Kaplan-Meier Estimates
Time frame: Basleline up to approximately 27 months
Overall Survival (OS) - Number of Participant Deaths
Time frame: Baseline up to approximately 27 months
Duration of Response (DOR)
Time frame: baseline up to approximately 30 months

Results and safety

Results posted to the registry on 8 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ceritinib 750 mg	47	0

Primary outcome: Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks

Time frame: Baseline up to approximately 16 weeks. Number (95% Confidence Interval). Unit: percentage of paarticipants

Measure	Ceritinib 750 mg n = 47
ORR (CR + PR) for all patients	6.4 (1.3 to 17.5)
CBR (CR + PR + SD) for all patients	19.1 (9.1 to 33.3)
ORR (CR + PR) for colorectal cancer patients	0.0 (0.0 to 30.8)
CBR (CR + PR + SD) for colorectal cancer	10.0 (0.3 to 44.5)

Population analysed: ORR and CBR was reported for all patients and for a subgroup of patients with colorectal cancer

Primary outcome: Number of Participants With Tumor Responses Utilizing RECIST 1.1 at Approximately 16 Weeks

Time frame: Baseline up to approximately 16 weeks. Count of participants. Unit: Participants

Measure	Ceritinib 750 mg n = 47
Complete response - all patients	0
Partial response - all patients	3
Stable disease- all patients	6
Progressive disease - all patients	32
Non-evaluable - all patients	6
Stable disease - Colorectal cancer patients	1
PD - Colorectal cancer patients	8
Non-evaluable - Colorectal cancer patients	1

Population analysed: tumor response was reported for all patients and for a subgroup of patients with colorectal cancer

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 27 months (treatment duration ranged from 0.2 to 26.9 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ceritinib 750 mg	16 of 47 (34%)	46 of 47 (97.9%)	5 of 47

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

21 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ceritinib in people with Tumors With Aberrations in ALK or ROS1, run by Novartis Pharmaceuticals at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) Utilizing RECIST 1.1 at Approximately 16 Weeks (time frame: Baseline up to approximately 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02186821.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.