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Neoplasms MalignantPhase 1NCT01121588

Studying An Investigational Drug Crizotinib (PF-02341066) In Non Non-Small Cell Lung Cancer Tumors That Are Positive For Anaplastic Lymphoma Kinase (ALK)

A Phase 1 study testing Crizotinib in people with Neoplasms Malignant, run by Pfizer at 21 sites in 7 countries.

Terminated

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

Official record
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Trial summary

This is a Phase 1 trial evaluating the safety and efficacy of crizotinib in patients with tumors except non-small cell lung cancer that are positive for ALK. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Neoplasms Malignant
What is being tested?
Crizotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
21 sitesin 7 countries
Study dates
22 Mar 2011to 7 Sep 2023
Phase
Phase 1
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 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • histologically or cytologically proven diagnosis of malignancy other than NSCLC
  • positive for translocation or inversion event involving the ALK gene locus
  • positive for ALK amplification events
  • positive for ALK activating point mutations

Who cannot join

  • mutations of amplifications involving the c-Met gene but not the ALK gene
  • concurrent treatment on another therapeutic clinical trial
  • prior therapy specifically directed against ALK

Trial locations and contacts

21 sites in 7 countries.

21 sites in 7 countries

United States9 sites

  • Highlands Oncology Group

    Fayetteville, Arkansas, 72703

  • Greenville Health System, Institute for Translational Oncology Research

    Greenville, South Carolina, 29605

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • OHSU Center for Health and Healing 2

    Portland, Oregon, 97239

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Highlands Oncology Group

    Rogers, Arkansas, 72758

  • Highland Oncology Group

    Springdale, Arkansas, 72762

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Japan3 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 811-1395

  • National Hospital Organization Nagoya Medical Center

    Nagoya, Aichi-ken, 460-0001

Other trials in Japan

China2 sites

  • Cancer Institute and Hospital, Chinese Academy of Medical Sciences

    Beijing, Chaoyang District, 100021

  • SUN Yat-Sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

Italy2 sites

  • Centro di Ricerca di Fase 1 ASST-Monza

    Monza, 20090

  • PO San Gerardo, ASST Monza-U.O Ematologia

    Monza, 20900

Other trials in Italy

Russia2 sites

  • GBOU VPO "First Saint-Petersburg State Medical University n.a.I.P Pavlov" Ministry of Health

    Saint Petersburg, 197022

  • Institute of Pedriatric Oncology, Hematology and Transplantation n.a R.M Gorbacheva

    Saint Petersburg, 197101

Other trials in Russia

South Korea2 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Taiwan1 site

  • National Taiwan University Hospital, Department of Internal Medicine

    Taipei, 100

Other trials in Taiwan

About this study

Official title: PHASE 1B OPEN-LABEL STUDY OF THE SAFETY AND CLINICAL ACTIVITY OF CRIZOTINIB (PF-02341066) IN TUMORS WITH GENETIC EVENTS INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK ) GENE LOCUS

This is a Phase 1 trial evaluating the safety and efficacy of crizotinib in patients with tumors except non-small cell lung cancer that are positive for ALK.

Being tested
Crizotinib
Keywords
neoplasm malignant, lymphoma, neuroblastoma, Crizotinib, anaplastic lymphoma kinase, ALK
Medical subject headings
Neoplasms, Lymphoma, Neuroblastoma

What participants receive

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

  • CrizotinibDrug

    Also called PF-02341066

    Crizotinib tablets, 250 mg BID, will be administered orally on a continuous dosing schedule

Study groups in NCT01121588
Study groupRoleWhat they receive
CrizotinibExperimentalNot described
Receives: Drug: Crizotinib

What is being measured

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

  1. Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs)

    An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care activity of daily living (ADL); Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

  2. Number of Participants With All-Causality TEAEs in the Pediatric Population

    An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication.Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

  3. Number of Participants With Treatment-Related TEAEs

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

  4. Number of Participants With Treatment-Related TEAEs in the Pediatric Population

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

  5. Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries)

    Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and clinical chemistry parameters were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

  6. Number of Participants With Laboratory Test Results Shifted From Grade <=2 At Baseline to Grade 3 or 4 Postbaseline (Hematology and Chemistries) in the Pediatric Population

    Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and chemistry laboratory assessments were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Unplanned laboratory test results were also included.

    Measured: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

  7. Objective Response Rate (ORR) - Percentage of Participants With Objective Response

    Percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) as determined by the investigators. CR = disappearance of all target lesions. PR = greater than equal to (>=) 30% decrease in sum of target lesions taking as reference baseline sum diameters. ORR based on Cheson criteria was defined similarly however, confirmation of response was not required. If participant had tumor response assessed only by RECIST or Cheson, then ORR was based on the single result. If tumor response was assessed by both RECIST and Cheson, then ORR was reported based on tumor response by Cheson criteria unless the Cheson has indeterminate result, in which case the RECIST result was reported. Participant(s) who did not have tumor assessment results from either RECIST 1.1 or Cheson criteria reported at baseline were to be excluded from the analysis.

    Measured: From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occured first (maximum 374 weeks)

Secondary outcomes (9)

  1. Progression-Free Survival (PFS) Based on Investigator Assessement

    PFS was defined as the time from the date of first dose of study medication to the date of the first documentation of objective tumor progression (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study [this includes the baseline sum if that is the smallest on study]). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression) or death on treatment due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. The median PFS was estimated using Kaplan-Meier method.

    Measured: From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occurs first (maximum 444 weeks)

  2. Duration of Response (DR) Based on Investigator Assessement

    DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. CR: disappearance of all lesions; any pathological lymph nodes (target lesions [TLs]) or non-target lesions (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters; DR (in weeks) was calculated as (first date of PD or death - first date of CR or PR +1)/7. The median DR was estimated using Kaplan-Meier estimates.

    Measured: From the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum 374 weeks)

  3. Percentage of Participants Surviving at 6 Months and 1 Year

    The probability of survival at 6 months and 1 year, respectively, after the date of the first dose based on the Kaplan-Meier estimate.

    Measured: At 6 months and 1 year after first dose

  4. Overall Survival (OS)

    OS is defined as the time from the date of first dose of study medication to the date of death due to any cause. OS (in months) was calculated as (date of death - date of first dose +1)/30.42. For participants still alive at the time of the analysis, for those who were lost to follow-up, and those who withdrew consent for additional follow up, the OS was censored on the last date that participants were known to be alive. Participants lacking data beyond the first dose had their OS censored at the date of first dose. The median OS was estimated using Kaplan-Meier method.

    Measured: From the first dose of study treatment to the date of death due to any cause (maximum 444 weeks)

  5. Steady-State Pre-dose Concentration (Ctrough) for Crizotinib on Day 1 of Cycles 2, 3 and 5

    Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.

    Measured: Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

  6. Steady-State Ctrough for PF-06260182 on Day 1 of Cycles 2, 3 and 5

    Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.

    Measured: Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

  7. Ctrough Ratios of PF-06260182 to Crizotinib on Day 1 of Cycles 2, 3 and 5

    Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection. The ratio is calculated as: (PF-06260182 concentration/464.33)/(Crizotinib concentration/450.34), where 464.33 is molecular weight for PF-06260182 and 450.33 is molecular weight for Crizotinib.

    Measured: Predose within -1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

  8. Number of Participants With ALK Genetic Events

    Number of participants with ALK translocation/fusion, amplification, mutation and overexpression at baseline assessed by technologies including fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), ALK Fusion partners assessed by FISH or PCR; ALK gene amplification assessed by FISH or array Comparative Genomic Hybridization (aCGH), ALK Mutation assessed by PCR or direct sequencing were reported.

    Measured: From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

  9. Phosphorylation Status of ALK in the Tumor Samples From Surgery or Biopsy Pre and Post Treatment

    Tumor sample was planned to be provided to the designated central laboratory for retrospective confirmation of ALK phosphorylation status by a Pfizer designated central laboratory. The molecular profiling results were planned to include ALK fusion/translocation, mutations, amplification and overexpression.

    Measured: From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

Timeline

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

  1. First posted12 May 2010 (estimated)
  2. Study start22 Mar 2011
  3. Primary completion7 Sep 2023
  4. Study completion7 Sep 2023

Why it stopped: Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01121588
Sponsor's protocol ID
A8081013
Other IDs
2010-022978-14
Status last verified
Dec 2024
First submitted
10 May 2010
Last updated
23 Jan 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crizotinib in people with Neoplasms Malignant, run by Pfizer at 21 sites in 7 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 4 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 23 Jan 2025. 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, Japan, China, Italy, Russia and 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 23 Jan 2025). 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?

Number of Participants With All-Causality Treatment-Emergent Adverse Events (TEAEs) (time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)). The study lists 7 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 NCT01121588.

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 23 Jan 2025.

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