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AzTrials

ALK-positive Non-small Cell Lung CancerPhase 2Ascend-7NCT02336451

A Phase II Study to Evaluate the Efficacy and Safety of Oral Ceritinib in Patients With ALK-positive NSCLC Metastatic to the Brain and/or to Leptomeninges

A Phase 2 study testing Ceritinib in people with ALK-positive Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 57 sites in 17 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This was a phase II, multi-center, open-label, five-arm study in which the efficacy and safety of oral ceritinib treatment was assessed in patients with NSCLC metastatic to the brain and/or to leptomeninges harboring a confirmed ALK rearrangement, using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ALK-positive Non-small Cell Lung Cancer
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
156 participants
Where
57 sitesin 17 countries
Study dates
1 Apr 2015to 6 Feb 2019
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

  • Histologically or cytologically confirmed diagnosis of metastatic NSCLC according to the 7th edition of the AJCC Cancer Staging Manual. In addition, the NSCLC must harbor an ALK rearrangement, as assessed using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above was not locally available, a test to confirm ALK rearrangement was to be performed by a Novartis designated central laboratory. Patients had to wait for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib
  • At least one extracranial measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion could only be counted as a target lesion if there was clear sign of progression since the irradiation.
  • Patients could or could not have neurological symptoms but must have been able to swallow and retain oral medication.
  • Patients had to be neurologically stable within at least 1 week prior to the first dose of study drug.
  • Patients could have received prior chemotherapy, crizotinib (other ALK inhibitors were not allowed), biologic therapy or other investigational agents.
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia were allowed to enter the study.
Show all 12Show fewer
  • Patient had life expectancy ≥ 6 weeks.
  • Patient had a WHO performance status 0-2.
  • Patients in Arm 1 to 4 had to also meet the following inclusion criteria:
  • Patients had to have active brain metastases from NSCLC, confirmed by Gadolinium-enhanced MRI without concomitant leptomeningeal carcinomatosis. Dose of steroids had to be stable for 5 days before the baseline brain MRI.
  • Patients in Arm 5 had to also meet the following inclusion criteria:
  • Patients must have been diagnosed with leptomeningeal carcinomatosis.

Who cannot join

  • Patients who needed whole brain radiation to control the brain metastases. Patients were not eligible unless treated brain lesions were progressive or new brain lesions were observed since the post whole brain radiation therapy MRI.
  • Planning of any brain local treatment (including but not limited to surgery, stereotactic radiosurgery, whole brain radiation, intrathecal chemotherapy) following the administration of the first dose of study drug.
  • Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion included the following: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
  • Patient had impairment of GI function or GI disease that could significantly alter the absorption of ceritinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
  • Patient was receiving unstable or increasing doses of corticosteroids.
  • Patient had other severe, acute, or chronic medical conditions including uncontrolled diabetes mellitus or psychiatric conditions or laboratory abnormalities that in the opinion of the investigator could increase the risk associated with study participation, or that could interfere with the interpretation of study results.

Trial locations and contacts

57 sites in 17 countries.

57 sites in 17 countries

Italy12 sites

  • Novartis Investigative Site

    Aviano, PN, 33081

  • Novartis Investigative Site

    Livorno, LI, 57124

  • Novartis Investigative Site

    Messina, ME, 98158

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Milan, MI, 20141

  • Novartis Investigative Site

    Monza, MB, 20900

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Parma, PR, 43100

  • Novartis Investigative Site

    Perugia, PG, 06129

  • Novartis Investigative Site

    Roma, RM, 00155

  • Novartis Investigative Site

    Verona, VR, 37126

Other trials in Italy

United States7 sites

  • Dana Farber Cancer Institute SC-12

    Boston, Massachusetts, 02215

  • The Ohio State University Comprehensive Cancer Center Ohio State University

    Columbus, Ohio, 43221

  • USC Kenneth Norris Comprehensive Cancer Center SC-3

    Los Angeles, California, 90033

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98105

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Stanford Universtiy Medical Center SC-5

    Stanford, California, 94304

  • Southwestern Regional Medical Center

    Tulsa, Oklahoma, 74133

Other trials in United States

Brazil7 sites

  • Novartis Investigative Site

    Barretos, São Paulo, 14784 400

  • Novartis Investigative Site

    Itajaí, Santa Catarina, 88301-229

  • Novartis Investigative Site

    Natal, Rio Grande do Norte, 59075 740

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 41253-190

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246 000

  • Novartis Investigative Site

    São Paulo, 01236 030

Other trials in Brazil

France6 sites

  • Novartis Investigative Site

    Marseille, Bouches Du Rhone, 13915

  • Novartis Investigative Site

    Paris, 75970

  • Novartis Investigative Site

    Rennes, 35043

  • Novartis Investigative Site

    Saint-Herblain Cédex, 44805

  • Novartis Investigative Site

    Strasbourg, 67091

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

Spain5 sites

  • Novartis Investigative Site

    Barcelona, 08041

  • Novartis Investigative Site

    Madrid, 28034

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28222

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

Other trials in Spain

South Korea3 sites

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, 03080

  • Novartis Investigative Site

    Seoul, 06351

Other trials in South Korea

Taiwan3 sites

  • Novartis Investigative Site

    Tainan, Taiwan ROC, 70403

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taipei, 11217

Other trials in Taiwan

United Kingdom3 sites

  • Novartis Investigative Site

    Birmingham, B9 5SS

  • Novartis Investigative Site

    London, SE1 9RT

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Germany2 sites

  • Novartis Investigative Site

    Bad Berka, 99437

  • Novartis Investigative Site

    Cologne, 50937

Other trials in Germany

Turkey (Türkiye)2 sites

  • Novartis Investigative Site

    Ankara, 06100

  • Novartis Investigative Site

    Istanbul, TUR, 34098

Other trials in Turkey (Türkiye)

Australia1 site

  • Novartis Investigative Site

    Auckland

Other trials in Australia

Belgium1 site

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Canada1 site

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Hong Kong1 site

  • Novartis Investigative Site

    Pokfulam, Hong Kong

Other trials in Hong Kong

Netherlands1 site

  • NKI-AVL, Department of Thoracic-Oncology

    Amsterdam, 1066 CX

Other trials in Netherlands

Russia1 site

  • Novartis Investigative Site

    Saint Petersburg, 192148

Other trials in Russia

Singapore1 site

  • Novartis Investigative Site

    Singapore, 169610

Other trials in Singapore

About this study

Official title: A Phase II, Multi-center, Open-label, Five-arm Study to Evaluate the Efficacy and Safety of Oral Ceritinib Treatment for Patients With ALK-positive Non-small Cell Lung Cancer (NSCLC) Metastatic to the Brain and/or to Leptomeninges

This was a phase II, multi-center, open-label, five-arm study in which the efficacy and safety of oral ceritinib treatment was assessed in patients with NSCLC metastatic to the brain and/or to leptomeninges harboring a confirmed ALK rearrangement, using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria). If documentation of ALK rearrangement as described above was not locally available, a test to confirm ALK rearrangement was performed by a Novartis designated central laboratory. Patients waited for the central laboratory result of the ALK rearrangement status before initiating treatment with ceritinib.

Read the detailed description

Approximately 160 patients diagnosed with ALK-positive metastatic NSCLC (according to the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual) and active lesions in the brain and/or diagnosed with leptomeningeal carcinomatosis were included in the study, approximately 40 patients in Arm 1 and Arm 2, approximately 30 patients in Arms 3 and Arm 4, and approximately 20 patients in Arm 5. Additional patients were enrolled in Arm 4 to achieve approximately 60 patients in Arms 3 and 4 together (i.e. ALKi naïve patients), if enrollment rate in Arm 3 was slow.

  • Arm 1 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain and with prior exposure to an ALKi.
  • Arm 2 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain but with prior exposure to an ALKi.
  • Arm 3 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously treated with radiation to the brain but with no prior exposure to an ALKi.
  • Arm 4 included patients with metastases in the brain without evidence of leptomeningeal carcinomatosis, previously untreated with radiation to the brain and with no prior exposure to an ALKi
  • Arm 5 included any patients with leptomeningeal carcinomatosis with or without evidence of active lesion at the baseline Gadolinium-enhanced brain MRI.

Note: Previous treatment with ALK inhibitors other than crizotinib was not allowed in Arms 1, 2, and 5.

Ceritinib was administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule. The treatment period started on Cycle 1 Day 1.

Complete tumor assessments including gadolinium enhanced brain MRI was repeated at Week 8 (on Cycle 3 Day 1) and every 8 weeks (i.e. every 2 cycles) thereafter or earlier if clinically indicated. Safety evaluations included (S)AEs, physical examination, vital signs, ECGs, laboratory parameters and WHO performance status. Blood and CSF samples for PK were also collected.

Being tested
Ceritinib
Keywords
ALK-positive, NSCLC, non-small cell lung cancer, brain metastasis, metastatic to the brain and/or to leptomeninges, ceritinib, LDK378, NSCLC metastatic to the brain, leptomeninges harboring a confirmed ALK rearrangement
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Brain Neoplasms

What participants receive

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

  • CeritinibDrug

    Also called LDK378

    LDK378 is a gelatin capsule, administered orally once daily at a dose of 750 mg (five 150 mg capsules) on a continuous dosing schedule on an empty stomach.

Study groups in NCT02336451
Study groupRoleWhat they receive
Arm 1 (PrALKi=Y, PrBRad=Y)ExperimentalParticipants with metastases in the brain without evidence of leptomeningeal carcinomatosis (LC), previously treated with radiation to the brain and with prior exposure to an Anaplastic lymphoma kinase inhibitor (ALK-I). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Receives: Drug: Ceritinib
Arm 2 (PrALKi=Y, PrBRad=N)ExperimentalParticipants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain but with prior exposure to an ALK-I. Previous treatment with ALK-I other than crizotinib was not allowed in this arm 2 as of protocol amendment 3 and had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Receives: Drug: Ceritinib
Arm 3 (PrALKi=N, PrBRad=Y)ExperimentalParticipants with metastases in the brain without evidence of LC, previously treated with radiation to the brain but with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Receives: Drug: Ceritinib
Arm 4 (PrALKi=N, PrBRad=N)ExperimentalParticipants with metastases in the brain without evidence of LC, previously untreated with radiation to the brain and with no prior exposure to an ALK-I. Participants in this arm had to present with active brain lesion defined as a lesion free of any local treatment (like stereotactic radiosurgery or whole brain radiation).
Receives: Drug: Ceritinib
Arm 5 (LepDis)ExperimentalParticipants had LC with or without evidence of active lesion at the baseline Gadolinium-enhanced brain magnetic resonance imaging (MRI). Previous treatment with ALK-I other than crizotinib was not allowed in this arm as of protocol amendment 3.
Receives: Drug: Ceritinib

What is being measured

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

  1. Overall Response Rate (ORR) Per Investigator Assessment

    Overall response rate (ORR) is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

Secondary outcomes (27)

  1. Disease Control Rate (DCR) Per Investigator Assessment

    DCR: percentage of parts. with best overall response of CR, PR or stable disease (SD) in the whole body, as assessed per RECIST 1.1 by investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: 43 months

  2. Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Investigator Assessment

    OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  3. Overall Intracranial Response Rate (OIRR) Per Modified RECIST 1.1 Per Blinded Independent Review Committee (BIRC) Assessment

    OIRR was calculated based on response assessments in the brain for patients having measurable brain metastases at baseline. OIRR was defined as the percentage of participants with a best overall confirmed response of CR or PR in the brain as assessed per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or decreased by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  4. Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment at Weeks 8 & 16

    IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: Week 8 and Week 16

  5. Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per Investigator Assessment - Overall

    IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by the Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: 43 months

  6. Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment at Weeks 8 & 16

    IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: Week 8 and Week 16

  7. Intracranial Disease Control Rate (IDCR) Per Modified RECIST 1.1 Per BIRC Assessment - Overall

    IDCR overall: percentage of participants with a best overall response of CR, PR, SD or non-CR/non-PD in the brain, as assessed per modified RECIST 1.1 by Investigator. This was applied to the brain only. CR: Disappearance of all non-nodal target \& non-target lesions. All lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: 43 months

  8. Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per Investigator Assessment

    TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  9. Time to Intracranial Tumor Response (TTIR) Per Modified RECIST 1.1 Per BIRC Assessment

    TTIR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the brain as assessed per modified RECIST 1.1 criteria for patients with measurable brain metastases at baseline. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  10. Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per Investigator Assessment

    Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. This was applied to the brain only. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  11. Duration of Intracranial Response (DOIR) by Modified RECIST 1.1 Per BIRC Assessment

    Defined as the time from the first documented response (PR or CR) in the brain to the date of the first documented disease progression in the brain or death due to any cause, amongst participants with measurable brain metastases at baseline and a confirmed response (PR or CR) in the brain as per modified RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  12. Overall Extracranial Response Rate (OERR) Per RECIST 1.1 Per Investigator & BIRC Assessment

    OERR was defined as the percentage of participants with a best overall confirmed response of CR or PR outside of the brain, as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  13. Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment - Overall

    EDCR overall was defined as the percentage of participants with a best overall response of CR, PR or SD outside of the brain as assessed per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: 43 months

  14. Extracranial Disease Control Rate (EDCR) Per RECIST 1.1 Per Investigator & BIRC Assessment at Weeks 8 & 16

    EDCR at weeks 8 \& 16: defined as percentage of parts. with CR, PR or SD outside of the brain at Wk 8 \& 16 extracranial tumor evaluations respectively, per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: Week 8 and Week 16

  15. Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per Investigator Assessment

    TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  16. Time to Extracranial Tumor Response (TTER) Per RECIST 1.1 Per BIRC Assessment

    TTER was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) outside of the brain as assessed per RECIST 1.1 criteria. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  17. Duration of Extracranial Response (DOER) Per RECIST 1.1 Per Investigator Assessment

    DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  18. Duration of Extracranial Response (DOER) Per RECIST 1.1 Per BIRC Assessment

    DOER was defined as the time from the first documented response (PR or CR) outside of the brain to the date of the first documented disease progression outside of the brain or death due to any cause, amongst patients with a confirmed response (PR or CR) outside of the brain per RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  19. Overall Response Rate (ORR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment

    Overall response rate ORR is defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  20. Disease Control Rate (DCR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment

    DCR: defined as percentage of participants with a best overall response of CR, PR or stable disease (SD) in the whole body, per RECIST 1.1 by BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), \& no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed and non-target lesions are not in progression or in complete response. SD: Neither sufficient shrinkage in the target lesion to qualify for PR or CR nor an increase in lesions which would qualify for PD \& non-target lesions are not in unequivocal progression.

    Measured: 43 months

  21. Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment

    TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed per RECIST 1.1 criteria per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  22. Time to Tumor Response (TTR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment

    TTR was defined as the time from the date of the first dose of ceritinib to the date of the first documented response (CR or PR) in the whole body as assessed by RECIST 1.1 criteria per BIRC assessment. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  23. Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per Investigator Assessment

    DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per Investigator. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  24. Duration of Response (DOR) (Whole Body) Per RECIST 1.1 Per BIRC Assessment

    DOR was defined as the time from the first documented response (PR or CR) to the date of the first documented disease progression or death due to any cause, amongst patients with a confirmed response (PR or CR) in the whole body per RECIST 1.1 per BIRC. CR: Disappearance of all non-nodal target and non-target lesions. In addition, all lymph nodes assigned a target or a non-target lesions must be non-pathological in size (< 10 mm short axis), and no new lesion is identified. PR: When all target lesions have disappeared or there is a decrease by at least 30% in the sum of diameter of all target lesions (taking as reference the baseline sum of diameters) is observed \& non-target lesions are not in progression or in complete response.

    Measured: 43 months

  25. Progression Free Survival (PFS) (Whole Body) Per RECIST 1.1 Per Investigator & BIRC Assessment

    PFS was defined as the time from the date of the first dose of ceritinib to the date of the first radiologically documented disease progression in the whole body per RECIST 1.1 or death due to any cause. A patient who had not progressed or died at the date of the analysis was censored at the time of the last adequate tumor evaluation on or before the cut-off date.

    Measured: 43 months

  26. Overall Survival (OS)

    OS was defined as time from the date of first dose of ceritinib to the date of death due to any cause. The OS time for patients who were alive at the end of the study or were lost to follow-up was censored at the date of last contact.

    Measured: 24 weeks

  27. Pharmacokinetics (PK) of Ceritinib in Study Population: Cmax & Cmin (Trough)

    Cmax is the maximum (peak) concentration of drug in plasma. Cmin is the minimum (trough) concentration of drug in plasma. Sparse blood samples for ceritinib PK evaluation in plasma were collected on C1D1 up to C6D1 from all patients who received at least one dose of investigational study treatment.

    Measured: Cmax: Cycle 2 Day 1 (C2D1); Cmin: C1D1, C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 - all 0hr (pre dose)

Timeline

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

  1. First posted13 Jan 2015 (estimated)
  2. Study start1 Apr 2015
  3. Primary completion6 Feb 2019
  4. Study completion6 Feb 2019

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02336451
Sponsor's protocol ID
CLDK378A2205
Other IDs
2014-000578-20, 2014
Acronym
Ascend-7
Status last verified
Apr 2020
First submitted
8 Jan 2015
Last updated
21 Apr 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Chow LQM, Barlesi F, Bertino EM, van den Bent MJ, Wakelee HA, Wen PY, Chiu CH, Orlov S, Chiari R, Majem M, McKeage M, Yu CJ, Garrido P, Hurtado FK, Arratia PC, Song Y, Branle F, Shi M, Kim DW. ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges. Clin Cancer Res. 2022 Jun 13;28(12):2506-2516. doi: 10.1158/1078-0432.CCR-21-1838.

    PubMed 35091443

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ceritinib in people with ALK-positive Non-small Cell Lung Cancer, run by Novartis Pharmaceuticals at 57 sites in 17 countries.

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 12 inclusion and 6 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: finished, as of the sponsor's last update on 21 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in Italy, United States, Brazil, France, Spain and 12 more countries. 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 21 Feb 2020). 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?

Overall Response Rate (ORR) Per Investigator Assessment (time frame: 43 months). 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 NCT02336451, which also lists 1 linked publication.

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 21 Apr 2020; AzTrials last refreshed its copy on 26 Oct 2026.

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