Clinical Trials /

PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer

NCT03439215

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer
  • Official Title: PF-06463922 for Crizotinib Pretreated ROS1 Positive Non-small-cell Lung Cancer: a Phase II Trial (PFROST)

Clinical Trial IDs

  • ORG STUDY ID: FoRT 01/2016
  • NCT ID: NCT03439215

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
LorlatinibLorlatinbLorlatinb Arm

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Lorlatinb ArmExperimentalEligible patients will be treated with Lorlatinib at the dose of 100 mg QD p.o.
  • Lorlatinib

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent;

          2. Male or female patient ages ≥ 18 years;

          3. Histologically/cytologically confirmed diagnosis of NSCLC with evidence of ROS1
             rearrangement;

          4. Possibility to perform a new tumor biopsy or tumor tissue collected at the time or
             after crizotinib failure;

          5. Patient pretreated with crizotinib with evidence of disease progression during
             crizotinib therapy;

          6. At least one radiological measurable disease according to RECIST criteria;

          7. At least 1 previous standard chemotherapy regimen;

          8. Performance status 0-2 (ECOG);

          9. Patient compliance to trial procedures

         10. Adequate bone marrow function (ANC ≥ 1.5x109/L, platelets ≥ 100x109/L, haemoglobin > 9
             g/dl);

         11. Adequate liver function (bilirubin < grade 2, transaminases no more than 3xULN/<5xULN
             in present of liver metastases);

         12. Normal level of alkaline phosphatase and creatinine;

         13. 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.

        Exclusion Criteria:

        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.

        -
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Correlation with additional tumor biomarkers in tumor tissue or blood

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fondazione Ricerca Traslazionale

Trial Keywords

  • ROS1 positive
  • NSCLC

Last Updated

January 28, 2019