Carcinoma, Non-Small-Cell LungPhase 2PFROSTNCT03439215
PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer
A Phase 2 study testing Lorlatinib in people with Carcinoma, Non-Small-Cell Lung, run by Fondazione Ricerca Traslazionale at 20 sites in Italy.
Trial summary
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Lorlatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 20 sitesItaly
- Study dates
- 13 Jun 2017to Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Written informed consent;
- Male or female patient ages ≥ 18 years;
- Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1 rearrangement;
- Possibility to perform a new tumor biopsy or tumor tissue collected at the time or after crizotinib failure;
- Patient pretreated with crizotinib with evidence of disease progression during crizotinib therapy;
- At least one radiological measurable disease according to RECIST criteria;
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- At least 1 previous standard chemotherapy regimen;
- Performance status 0-2 (ECOG);
- Patient compliance to trial procedures
- Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥ 100x109/L, haemoglobin > 9 g/dl);
- Adequate liver function (bilirubin < grade 2, transaminases no more than 3xULN/<5xULN in present of liver metastases);
- Normal level of alkaline phosphatase and creatinine;
- If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [intrauterine contraceptive device (IUD), birth control pills, or barrier device] during and for ninety (90) days after end of treatment.
Who cannot join
- 1. No ROS1 rearrangement 2. No previous therapy with crizotinib; 3. No evidence of crizotinib failure; 4. No post-crizotinib tumor tissue available; 5. Absence of any measurable lesions; 6. No previous chemotherapy; 7. Concomitant radiotherapy or chemotherapy; 8. Symptomatic brain metastases; 9. Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin; 10. Predisposing factors for acute pancreatitis (e.g., uncontrolled hyperglycaemia, current gallstone disease, alcoholism); 11. History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis); 12. Pregnancy or lactating female; 13. Other serious illness or medical condition potentially interfering with the study.
- -
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Italy20 sites
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
Arezzo, 52100
Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"
Avellino, 83100
IRCCS Istituto Tumori Giovanni Paolo II
Bari, 70124
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
Genova, 16132
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
Meldola, Forlì- Cesena, 47014
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
Milan, 20141
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
Modena, 41124
A.O. San Gerardo
Monza, 20900
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Naples, 80131
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
Negrar, Verona, 37024
Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
Padova, 35128
Casa di Cura La Maddalena- U.O. Oncologia medica
Palermo, 90146
Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
Parma, 43126
Azienda Ospedaliera di Perugia- S.C. Oncologia Medica
Perugia, 06132
Ospedale di Ravenna- Oncologia Medica
Ravenna, 48121
Ospedale "Infermi" Rimini
Rimini, 47900
ASST della Valle Olona - Ospedale di Saronno
Saronno, 21047
A.O.U. San Luigi Gonzaga
Torino, 10043
Azienda ULSS 9 TREVISO-UOC Oncologia Medica
Treviso, 31100
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
Verona, 37134
About this study
Official title: PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer: a Phase II Trial (PFROST)
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
Read the detailed description
PF-06463922 is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration. The results showed that PF-06463922 is most potent against ROS1 and ALK, with selectivity ratios >100-fold for ROS1 over the 204 kinases tested. A recent study has investigated the activity of PF-06463922 against the crizotinib-resistant ROS1G2032R mutation in both recombinant enzyme and cell-based assays. PF-06463922 effectively inhibited the catalytic activity of recombinant ROS1G2032R and the CD74-ROS1G2032R fusion kinase in BaF3 cells. This effect translated directly into an antiproliferative response. These results, together with its exquisite ROS1 potency and ability to suppress the resistant ROS1 mutations, supports the clinical evaluation of PF-06463922 in ROS1-positive NSCLC, including patients who have developed resistance to crizotinib because of the acquired G2032R mutation and/or brain metastases.
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Lorlatinib
- Keywords
- ROS1 positive, NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
Also called Lorlatinb
Lorlatinib is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration.
| Study group | Role | What they receive |
|---|---|---|
| Lorlatinb Arm | Experimental | Eligible patients will be treated with Lorlatinib at the dose of 100 mg QD p.o. Receives: Drug: Lorlatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Secondary outcomes (4)
Progression-free survival (PFS), The length of time during and after the treatment of a disease,that a patient lives with the disease but it doesn't get worse.
Progression-free survival (PFS) will be calculated from the time between the baseline/start of treatment visit to the time of first occurrence of progressive disease (PD) or death from any cause. Patients who have neither progressed nor died at time of analysis will be censored at the date of last tumor assessment where non progression was documented (i.e. CR, PR or SD)
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Overall Survival (OS): Time from the start of treatment until death from any cause
Overall survival (OS) will be calculated from the time between the baseline/start of treatment visit to the date of death, irrespective of the cause of death. Patients still alive at the time of analysis will be censored at the date they were last known to be alive
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Patients will be closely monitored for signs and symptoms of potential adverse events, and will undergo frequent laboratory tests to assess lipids, pancreas, liver, kidney, and haematological function.
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Correlation with additional tumor biomarkers in tumor tissue or blood
Correlation with additional tumor biomarkers in tumor tissue or blood
Measured: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start13 Jun 2017
- Primary completionJun 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Ricerca Traslazionale
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Research Technology S.r.l.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439215
- Sponsor's protocol ID
- FoRT 01/2016
- Acronym
- PFROST
- Status last verified
- Jul 2021
- First submitted
- 1 Feb 2018
- Last updated
- 19 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer: a Phase II Trial (PFROST)
- ClinicalTrials.gov ID
- NCT03439215
- Acronym / sponsor ID
- PFROST / FoRT 01/2016
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- ROS1 positive, NSCLC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Fondazione Ricerca TraslazionaleUniversity, hospital or other
- Collaborators
- Clinical Research Technology S.r.l.
- Study start
- 13 Jun 2017 (actual)
- Primary completion
- Jun 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 20 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
Detailed description
PF-06463922 is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration. The results showed that PF-06463922 is most potent against ROS1 and ALK, with selectivity ratios >100-fold for ROS1 over the 204 kinases tested. A recent study has investigated the activity of PF-06463922 against the crizotinib-resistant ROS1G2032R mutation in both recombinant enzyme and cell-based assays. PF-06463922 effectively inhibited the catalytic activity of recombinant ROS1G2032R and the CD74-ROS1G2032R fusion kinase in BaF3 cells. This effect translated directly into an antiproliferative response. These results, together with its exquisite ROS1 potency and ability to suppress the resistant ROS1 mutations, supports the clinical evaluation of PF-06463922 in ROS1-positive NSCLC, including patients who have developed resistance to crizotinib because of the acquired G2032R mutation and/or brain metastases.
This is a phase II study assessing response rate to PF-06463922 in patients with ROS1 translocation resistant to previous crizotinib therapy. Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal. Disease assessment will be performed every 8 weeks according to RECIST criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lorlatinb Arm | Experimental | Drug: LorlatinibEligible patients will be treated with Lorlatinib at the dose of 100 mg QD p.o. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent;
- Male or female patient ages ≥ 18 years;
- Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1 rearrangement;
- Possibility to perform a new tumor biopsy or tumor tissue collected at the time or after crizotinib failure;
- Patient pretreated with crizotinib with evidence of disease progression during crizotinib therapy;
Key exclusion criteria (2 listed)
- 1. No ROS1 rearrangement 2. No previous therapy with crizotinib; 3. No evidence of crizotinib failure; 4. No post-crizotinib tumor tissue available; 5. Absence of any measurable lesions; 6. No previous chemotherapy; 7. Concomitant radiotherapy or chemotherapy; 8. Symptomatic brain metastases; 9. Diagnosis of any other malignancy during the last 5 years, except for in situ carcinoma of cervix uteri and squamous cell carcinoma of the skin; 10. Predisposing factors for acute pancreatitis (e.g., uncontrolled hyperglycaemia, current gallstone disease, alcoholism); 11. History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis (but not history of prior radiation pneumonitis); 12. Pregnancy or lactating female; 13. Other serious illness or medical condition potentially interfering with the study.
- -
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 |
|---|---|---|
| LorlatinibAlso: LorlatinbLorlatinib is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration. | Drug | Lorlatinb Arm |
Primary outcome
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
4 secondary outcomes
Progression-free survival (PFS), The length of time during and after the treatment of a disease,that a patient lives with the disease but it doesn't get worse.
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Overall Survival (OS): Time from the start of treatment until death from any cause
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Correlation with additional tumor biomarkers in tumor tissue or blood
Time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2021.
- PFROST trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
20 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 Lorlatinib in people with Carcinoma, Non-Small-Cell Lung, run by Fondazione Ricerca Traslazionale at 20 sites in Italy.
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 13 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 19 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Italy. 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?
Results are not available in the source record.
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?
Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib (time frame: From date of the first enrolment until the date of last documented progression or date of death from any cause, assessed up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jul 2021.