Clinical trial NCT03439215: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: ROS1 positive
NSCLC
Lead sponsor: Fondazione Ricerca Traslazionale
Sponsor class: OTHER
Collaborators: name: Clinical research technology Srl
First posted: 2018-02-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.

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.

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Primary outcomes:
measure: Response rate to PF-06463922 in patients with ROS1 translocation resistant to crizotinib
timeFrame: 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:
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.
timeFrame: 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
measure: Overall Survival (OS): Time from the start of treatment until death from any cause
timeFrame: 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
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 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
measure: Correlation with additional tumor biomarkers in tumor tissue or blood
timeFrame: 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
Other outcomes:
Locations:
city: Meldola
country: Italy
facility: IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica
state: Forlì- Cesena
city: Negrar
country: Italy
facility: Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica
state: Verona
city: Arezzo
country: Italy
facility: Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8
city: Avellino
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
city: Genova
country: Italy
facility: IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia - Divisione di Oncologia Toracica
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio
city: Monza
country: Italy
facility: A.O. San Gerardo
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena- U.O. Oncologia medica
city: Parma
country: Italy
facility: Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia- S.C. Oncologia Medica
city: Ravenna
country: Italy
facility: Ospedale di Ravenna- Oncologia Medica
city: Rimini
country: Italy
facility: Ospedale "Infermi" Rimini
city: Saronno
country: Italy
facility: ASST della Valle Olona - Ospedale di Saronno
city: Torino
country: Italy
facility: A.O.U. San Luigi Gonzaga
city: Treviso
country: Italy
facility: Azienda ULSS 9 TREVISO-UOC Oncologia Medica
city: Verona
country: Italy
facility: Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica
Study officials:
References: