Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1

NCT02034981 | Completed Phase 2 DMC

• 2 other identifiers: UC-0105/13032013-000885-13
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

Brief Summary

This is a biology driven, trans-tumoral, multicentric phase II trial assessing the efficacy and the safety of the targeted agent crizotinib as a monotherapy in 23 cohorts of patients with identified activating molecular alterations in the crizotinib target genes. A cohort is defined by a pathology and a crizotinib-target alteration (eg gastric cancer with MET amplification). For each cohort a two-stage design will be implemented. In the situation where expected accrual allows for a sufficient number of patients to be accrued, the alpha and beta errors will be fixed at 10%. However, in very rare diseases, such as inflammatory myofibroblastic tumor (IMT), neuroblastoma, glioblastoma, and rhabdomyosarcoma (RMS), it is anticipated that the target number may not be achievable in a reasonable timeframe; for these cohorts, the alpha and beta errors will be fixed at 15%. Consequently three different statistical designs will be a priori considered according to the expected response rate and incidence.

Conditions

Hematologic Cancers; Solid Tumors; Metastatic Cancer

Keywords

metastatic or unresectable locally advanced malignancies.; genomic alterations.; biological crizotinib targets (ALK, MET, ROS1, RON, AXL).

Outcome Measures

Primary Outcomes (1)

• The efficacy of crizotinib as a single agent across diverse type of tumors guided by the presence of identified activating molecular alterations in the crizotinib target genes, per cohort, per pathology, and per target.

  Anti-tumor activity of crizotinib, as the primary objective of the trial, will be carried out by the determination of the objective response assessed in each cohort defined by a pathology associated with a crizotinib target alteration. The objective response is defined as either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The objective response after 2 cycles (8 weeks) will be reported to define a success in the 2-stage design.

  Determined after 8 weeks (2 cycles) of treatment

Secondary Outcomes (5)

• The safety profile of crizotinib.

  Safety profile will be assessed during the whole treatment period (6 months expected in average) followed by a 2-year post-treatment follow-up period, and reported during the visits scheduled by the study flow chart

• Disease control rate

  After 8 weeks (2 cycles) and 16 weeks (4 cycles) of treatment

• response duration

  interval between the objective response (CR or PR) and time of progression, recurrence or death

• Progression-free survival

  from registration until time of disease progression or death

• Overall survival

  from registration until date of death

Study Arms (1)

CRIZOTINIB

EXPERIMENTAL

All eligible patients entering the study will receive oral crizotinib as monotherapy

Drug: Crizotinib

Interventions

Crizotinib DRUG

Patients will receive oral crizotinib, daily continuously, until progression or unacceptable toxicity develops. -250 mg twice daily for adults ≥ 18 years of age * 280 mg/m² twice daily for children and adolescents aged from 1 to 17 (except ALCL). * 165 mg/m² twice daily for ALCL patients aged from 1 to 17.

Also known as: XALKORI

CRIZOTINIB

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female ≥ 1 year of age
• unresectable locally advanced or metastatic malignant tumor of any histological type (but NSCLC with an ALK translocation) and not amenable to any other validated therapeutic option. ( for pediatrics a relapse after a first well-conducted standard treatment or a situation without any standard treatment and a survival \<10%).
• one proven specific alterations among ALK, MET, RON and ROS1 genes determined on the primary and/or the metastatic lesion
• Measurable disease according to RECIST 1.1
• For patients with primary cerebral tumors (adults or children), measurable disease defined by bi-dimensional measurements : two perpendicular diameters of at least 10 mm on CT or MRI scan, outside of a previously radiated field within the last 3 months, to observe pseudoprogression
• hematologic function (ANC ≥ 1.0x10⁹/L, platelets ≥ 75x10⁹/L, platelets ≥ 50x10⁹/L for ALCL with bone marrow involved ; platelets ≥ 100x10⁹/L for primary or secondary cerebral tumors; Hb ≥ 8g/L), renal function (creat cl ≥ 50 mL/min Cockcroft and Gault) and hepatic function (serum bilirubin ≤ 1.5x ULN unless due to Gilbert's syndrome ; ASAT and ALAT ≤ 5x ULN if liver metastasis or ≤ 3x ULN if liver metastasis with advanced fibrosis (FibroTest\>0.48) or ≤ 3x ULN without liver metastasis)
• normal values for calcium, magnesium and potassium levels
• able to swallow and retain oral medication
• ECOG Performance Status of 0 to 2, or Karnofsky scale \> 50 % or Lansky Play scale (\< 12 years) \> 50%, (for CNS tumors, the neurological deficiency due to the disease itself)
• Life expectancy ≥ 3 months
• NSCLC patients ALK translocations
• Patient eligible for a clinical trial with an anticancer drug (including crizotinib) targeting the same molecular alteration open to accrual in France.
• alteration limited to an overexpression of ALK, MET, RON, ROS1 or any other crizotinib-target. Only patients with ALCL are eligible if ALK is positive by immunohistochemistry
• Patients with primary or secondary central nervous system disease
• Previous treatment with crizotinib

Sponsors & Collaborators

• UNICANCER: lead
• National Cancer Institute, France: collaborator
• Fondation ARC: collaborator
• Pfizer: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, Île-de-France Region, 94805, France

Location

Related Publications (3)

• Brugieres L, Cozic N, Houot R, Rigaud C, Sibon D, Arfi-Rouche J, Bories P, Cottereau AS, Delmer A, Ducassou S, Garnier N, Lamant L, Leruste A, Millot F, Moalla S, Morschhauser F, Nolla M, Pagnier A, Reguerre Y, Renaud L, Schmitt A, Simonin M, Verschuur A, Hoog Labouret N, Mahier Ait Oukhatar C, Vassal G. Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSe-crizotinib trial. Eur J Cancer. 2023 Sep;191:112984. doi: 10.1016/j.ejca.2023.112984. Epub 2023 Jul 17.

  PMID: 37549532 DERIVED

• Aparicio T, Cozic N, de la Fouchardiere C, Meriaux E, Plaza J, Mineur L, Guimbaud R, Samalin E, Mary F, Lecomte T, Gomez-Roca C, Haineaux PA, Gratet A, Selves J, Menu Y, Colignon N, Johnson L, Legrand F, Vassal G. The Activity of Crizotinib in Chemo-Refractory MET-Amplified Esophageal and Gastric Adenocarcinomas: Results from the AcSe-Crizotinib Program. Target Oncol. 2021 May;16(3):381-388. doi: 10.1007/s11523-021-00811-8. Epub 2021 Apr 13.

  PMID: 33847874 DERIVED

• Moro-Sibilot D, Cozic N, Perol M, Mazieres J, Otto J, Souquet PJ, Bahleda R, Wislez M, Zalcman G, Guibert SD, Barlesi F, Mennecier B, Monnet I, Sabatier R, Bota S, Dubos C, Verriele V, Haddad V, Ferretti G, Cortot A, De Fraipont F, Jimenez M, Hoog-Labouret N, Vassal G. Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSe phase II trial. Ann Oncol. 2019 Dec 1;30(12):1985-1991. doi: 10.1093/annonc/mdz407.

  PMID: 31584608 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Study Officials

• Gilles VASSAL

  Gustave Roussy, Villejuif

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2013
• First Posted: January 14, 2014
• Study Start: August 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: December 6, 2023
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

FR (1)