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

NCT ID: NCT03439215

Last Updated: 2021-07-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-13
• Study Completion Date: 2022-06-30

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lorlatinb Arm

Eligible patients will be treated with Lorlatinib at the dose of 100 mg QD p.o.

Group Type: EXPERIMENTAL

Lorlatinib

Intervention Type: DRUG

Lorlatinib is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration.

Interventions

Lorlatinib

Lorlatinib is a novel small-molecule ROS1/ALK inhibitor that was optimized for robust brain penetration.

Intervention Type: DRUG

Other Intervention Names

Lorlatinb

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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• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical research technology Srl

UNKNOWN

Sponsor Role: collaborator

Fondazione Ricerca Traslazionale

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica

Meldola, Forlì- Cesena, Italy

Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica

Negrar, Verona, Italy

Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8

Arezzo, , Italy

Azienda Ospedaliera di Rilievo Nazionale "S.G. Moscati"

Avellino, , Italy

IRCCS Istituto Tumori Giovanni Paolo II

Bari, , Italy

IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari

Genova, , Italy

Istituto Europeo di Oncologia - Divisione di Oncologia Toracica

Milan, , Italy

A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio

Modena, , Italy

A.O. San Gerardo

Monza, , Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Istituto Oncologico Veneto IRCCS- UOS Oncologia Toracica UOC. Oncologia Medica 2

Padua, , Italy

Casa di Cura La Maddalena- U.O. Oncologia medica

Palermo, , Italy

Azienda Ospedaliera Universitaria di Parma- Struttura Complessa di Oncologia Medica

Parma, , Italy

Azienda Ospedaliera di Perugia- S.C. Oncologia Medica

Perugia, , Italy

Ospedale di Ravenna- Oncologia Medica

Ravenna, , Italy

Ospedale "Infermi" Rimini

Rimini, , Italy

ASST della Valle Olona - Ospedale di Saronno

Saronno, , Italy

A.O.U. San Luigi Gonzaga

Torino, , Italy

Azienda ULSS 9 TREVISO-UOC Oncologia Medica

Treviso, , Italy

Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica

Verona, , Italy

Countries

Italy

Related Links

https://www.cr-technology.com/fort/?studio_clinico=pfrost

PFROST trial

Other Identifiers

FoRT 01/2016

Identifier Type: -

Identifier Source: org_study_id