PF-06463922 for crizotinib pretreated ROS1 positive non-small-cell lung cancer: a phase II Trial (PFROST)

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 20

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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, hypersentivity 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy and safety and tolerability of PF-06463922 in crizotinib-pre-treated metastatic non-small-cell lung cancer with ROS1 translocation.;Secondary Objective: To evaluate the progression-free survival (PFS), Overall Survival and Toxicity ;Primary end point(s): Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib;Timepoint(s) of evaluation of this end point: 24 month

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): ¿Progression-free survival (PFS)<br>¿Overall Survival (OS)<br>¿Toxicity<br>¿Correlation with additional tumor biomarkers in tumor tissue or blood<br>;Timepoint(s) of evaluation of this end point: Eligible patients will be treated with the study drug until disease progression, unacceptable toxicity or patient refusal.

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