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AZD2014 and Weekly Paclitaxel in Squamous NSCLC

4 de junho de 2018 atualizado por: AstraZeneca

A Phase 2a, Multi-centre, Single-arm Trial of the Combination of AZD2014 and Weekly Paclitaxel in Patients With Relapsed or Refractory Squamous Non-Small Cell Lung Cancer After At Least One Line of Prior Therapy

Open--label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC)

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Descrição detalhada

This is an open-label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of the combination of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC) that is relapsed or refractory to conventional treatment after at least 1 prior treatment with standard of care (SOC) and for whom weekly paclitaxel treatment is an appropriate treatment choice.

The study will simultaneously enrol patients to the following two groups. Group A (intensive PK) will enrol 10 evaluable patients for an intra-patient evaluation of the impact of paclitaxel on exposure to AZD2014, and the impact of AZD2014 on exposure to paclitaxel via intensive PK sampling and non-compartmental PK analysis techniques (NCA). Group B (sparse PK) will enrol 30 patients and sparse sampling and population PK modelling techniques will be employed to estimate exposure to AZD2014 when administered in combination with a weekly paclitaxel dosing regimen. The efficacy and safety of the AZD2014 and weekly paclitaxel combination will be evaluated in all 40 patients using RECIST 1.1, observation of AEs/SAEs and use of conventional safety parameters.

Eligible patients will receive study treatment consisting of a single weekly paclitaxel infusion (80 mg/m2) on Day 1 of each week and twice daily (BD) 50 mg doses of AZD2014 on the first 3 days each week for 6 weeks [except Group A patients in Week 1 of Cycle 1 who will take 50 mg BD doses of AZD2014 on Days 3, 4 and 5 (or Days 4, 5 and 6) to accommodate PK sampling], followed by a break from treatment when no paclitaxel or AZD2014 will be given. This 7-week schedule composes one cycle of treatment. AZD2014 will be administered as oral tablets to fasted patients (i.e., no food 2 hours before and 1 hour after each dose). Patients will receive up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.

Tipo de estudo

Intervencional

Inscrição (Real)

11

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Alemanha
      • Gauting, Alemanha, 82131
        • Research Site
  • Espanha
      • Barcelona, Espanha, 08035
        • Research Site
      • Girona, Espanha, 17007
        • Research Site
  • Estados Unidos
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02215
        • Research Site
    • Michigan
      • Detroit, Michigan, Estados Unidos, 48201
        • Research Site
    • Pennsylvania
      • Hershey, Pennsylvania, Estados Unidos, 17022
        • Research Site
    • Texas
      • Dallas, Texas, Estados Unidos, 75251
        • Research Site

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos a 130 anos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Histologically or cytologically proven squamous non-small cell lung cancer (NSCLC) where treatment with weekly paclitaxel is an appropriate treatment option.
  2. Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment.
  3. Measurable disease by RECIST v1.1 criteria
  4. Life expectancy of at least 12 weeks.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

  1. Radiotherapy (except for palliative reasons), chemotherapy, endocrine therapy, or immunotherapy during the previous 3 weeks (4 weeks for investigational medicinal products and 6 weeks for nitrosoureas and Mitomycin-C) before treatment.
  2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities which, in the opinion of the Investigator, should not exclude the patient.
  3. Known leptomeningeal involvement, brain metastases or spinal cord compression.
  4. History of hypersensitivity (> Grade 2) to active or inactive excipients of AZD2014, drugs containing Cremophor, taxanes or structurally/chemically similar drugs
  5. Current refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow formulated product or previous significant bowel resection that would preclude adequate absorption of AZD2014
  6. Patients with Diabetes Type I or uncontrolled Type II (HbA1c > 59 mmol/mol assessed locally) as judged by the Investigator
  7. Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study and from which the patient has not yet recovered

  8. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening (with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which require at least 14 days prior to screening), defined as:

    • Absolute neutrophil count 1500 cells/mm3 (1.5 x 109/L)
    • Platelet count 100.000 cells/mm3 (100 x 109/L)
    • Haemoglobin 9.0 g/dL

  9. Adequate hepatic and renal function defined as:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) 2.5 x upper limit of normal (ULN) if no demonstrable liver metastases or 5 x ULN in the presence of liver metastases
    • Alkaline phosphatase (ALP) < 5 x ULN
    • Serum bilirubin 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
    • Estimated Creatinine Clearance 50 ml/min (Cockcroft-Gault) or serum creatinine 1.5 x ULN

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Open-label AZD2014
Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel
Medicamento: Open-label AZD2014
Dual TORC1/TORC2 inhibitor
Medicamento: paclitaxel
Taxane

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes
Prazo: From first dose until disease progression (Approximately 3 months)
Calculation of the percentage of patient who have a Complete Response or Partial Response to treatment which is confirmed by a repeat assessment 4 weeks later
From first dose until disease progression (Approximately 3 months)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Number of Patients Who Experienced at Least One Adverse Event (AE) or Serious Adverse Event (SAE)
Prazo: Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)

The safety and tolerability of AZD2014 with weekly paclitaxel as assessed with the collection of Adverse Events and Serious Adverse Events as reported during clinic visits. In addition, clinical assessments were made throughout the on treatment period including blood test for chemistry, haematology, and blood clotting. In addition to clinical observations such as vital signs, and cardiac function through the use of ECG.

Any findings from the above assessments which were considered to be abnornal and clinically significant by the doctor were reported as (AEs or SAEs).
Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)
Overall Survival: Median Number of Days Between the First Dose and End of Life Due to Any Cause
Prazo: From first dose until end of life (Approx 9 months)
Assessment of the duration of overall survival in weeks through direct patient follow-up. Any patient not known to have died at the time of analysis censored at the last recorded date the patient was known to be alive
From first dose until end of life (Approx 9 months)
Best Objective Response: Number of Patients Who Experienced a Best Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not-Evaluable (NE), Through Measurement of Tumour Lesion Sizes.
Prazo: From Baseline until Disease Progression (Approx 3 months)
Per Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed through imaging (CT or MRI scan) or clinical examination; Complete Response (CR): Disappearance of all target lesions; Partial Response (PR) >=30% decrease in sum of target lesion longest diameter; Progressive Disease >=20% increase in sum of target lesion longest diameter; Stable Disease (SD) increase or decrease amounting to neither PR or PD. Overall tumour assessment based on quantitative assessment of target lesions and qualitative assessment of non-target lesions in line with RECIST criteria.
From Baseline until Disease Progression (Approx 3 months)
Duration of Response: Median Number of Days From the Date of First Documented Response Until the Date of Documented Progression Through Measurement of Tumour Lesion Sizes
Prazo: From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)
Assessment of the duration of tumour response through assessment of tumour lesions by RECIST 1.1 criteria. Response is defined as the point at which the criteria for Partial Response (PR) was met) >=30% decrease in sum of target lesion longest diameter. Progression is defined as the point at which the criteria for Progressive Disease (PD) was met >=20% increase in sum of target lesion longest diameter, or until end of life.
From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)
Disease Control Rate: Percentage of Patients Who Achieve Partial Response, Complete Response or Stable Disease Through Assessment of Tumour Lesion Sizes
Prazo: From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks
Assessment of the disease control rate, percentage of patients who experience a response through assessment of tumour lesions by RECIST 1.1 criteria
From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks
Change in Tumour Size: Median Percentage Change in Tumour Size in mm by Measurement of Tumour Lesion Sizes
Prazo: From baseline until documented progression (Approx 3 months)
Assessment of the degree of tumour response through measurement of the change in tumour lesion sizes
From baseline until documented progression (Approx 3 months)
Progression Free Survival: Median Number of Days Between Start of Dosing Until Objective Disease Progression Through Measurement of Tumour Lesion Sizes
Prazo: From date of first dose until documented progression or end of life (Approx 3 months)
Assessment of the duration of progression free survival through assessment of tumour lesions by RECIST 1.1 criteria
From date of first dose until documented progression or end of life (Approx 3 months)
Evaluate the Effect of the Combination of AZD2014 and Paclitaxel on Pharmacokinetics Assessment of Cmax
Prazo: Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8
To determine the effect of co-administration of paclitaxel on the PK of oral AZD2014 and the effect of co administration of oral AZD2014 on the PK of paclitaxel (Group A) by: PK parameters for each in the presence and absence of the other by intensive PK sampling and NCA techniques.
Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8
Estimated Pharmacokinetic Exposure to AZD2014 Through the Use of Population PK Modelling
Prazo: Assessment at multiple timepoints in Group B patients between study day 1 and day 3. Samples will be taken at 3 points on day 1 and at predose and at a further 2 points on day 3
Group B patients: PK parameters for AZD2014 estimated from a sparse PK sampling regimen and use of population PK modelling techniques (may be reported outside the clinical study report (CSR))
Assessment at multiple timepoints in Group B patients between study day 1 and day 3. Samples will be taken at 3 points on day 1 and at predose and at a further 2 points on day 3

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

AstraZeneca

Investigadores

  • Investigador principal: Chandra P Belani, MD, Hershey Medical Center

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

15 de abril de 2015

Conclusão Primária (Real)

29 de dezembro de 2016

Conclusão do estudo (Real)

29 de dezembro de 2016

Datas de inscrição no estudo

Enviado pela primeira vez

7 de março de 2015

Enviado pela primeira vez que atendeu aos critérios de CQ

26 de março de 2015

Primeira postagem (Estimativa)

31 de março de 2015

Atualizações de registro de estudo

Última Atualização Postada (Real)

3 de julho de 2018

Última atualização enviada que atendeu aos critérios de controle de qualidade

4 de junho de 2018

Última verificação

1 de junho de 2018

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • D2274C00001

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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