Open-label Study in Patients With Metastatic NSLC Treated With Cisplatin, Gemcitabine and Bevacizumab

NCT02316327 | Completed Phase 4

• 2 other identifiers: IMPACT2012-000459-15
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Classically the evaluation of response in lung cancer has been based in comparing pre \& post treatment tumour volume by means of studying changes in the diameter of the selected target lesions by RECIST. The introduction of new targeted drugs creates the need of a different response assessment. Functional imaging techniques are able to study in vivo physiological processes of angiogenesis. Therefore, dynamic techniques may be more appropriate for assessing response to antiangiogenic drugs, whose mechanism of action is focused on tumor's vasculature normalization. Preliminary studies have demonstrated significant and very early changes in indirect vasculature parameters such as flow, blood volume and tumor perfusion with vascular-targeting agents. These techniques may be useful for selecting patients who are going to benefit from antiangiogenic therapy by an early evaluation of response by means of functional imaging method. PURPOSE: IMPACT is an open-label, single arm phase II/IV study to evaluate the predictive value and early radiologic response or perfusion computed tomography (CT) in patients diagnosed with unresectable advanced, metastatic or recurrent non-squamous NSCLC treated with bevacizumab in combination with chemotherapy.

Conditions

Non-Small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (1)

• To evaluate blood supply, blood volume, time to peak flow increase and permeability and relation with the objective response to treatment (RC+RP)

  The results on baseline and day 7 to treatment in terms of blood suply, blood volume, time of peak flow increase and permeability and relation with the objective (RC+RP) at day 42.

Secondary Outcomes (4)

• To evaluate the response to treatment in terms of blood supply, blood volume and time to peak flow increase and permeability.

  To evaluate at day +42 the response to treatment in terms of blood supply, blood volume and time to peak flow increase and permeability.

• To evaluate the blood supply, blood volume, time to peak flow increase, permeability related with PFS and OS.

  To evaluate the blood fluid, blood volume, time to peak flow increase, permeability at baseline visita related with PFS and OS.

• To evaluate the response to treatment at day +7 and +42 in terms of blood fluid, blood volume, time to peak flow increase, permeability at baseline visit related with PFS and OS.

  To evaluate the response to treatment at day +7 and +42 in terms the blood fluid, blood volume, time to peak flow increase, permeability at baseline visita related with PFS and OS.

• The safety of the treatment following NCI-CTC AE (version 4.0)

  The safety of the treatment following NCI-CTC AE (version 4.0)

Study Arms (1)

gemcitabine, cisplatin and bevacizumab

EXPERIMENTAL

Bevacizumab will be given by I.V infusion at the dose of 7.5 mg/kg on days 1 every 21 days Cisplatin 80 mg/m2 I.V on day 1 Gemcitabine 1250 mg/m2 I.V on day 1 \& 8 Treatment cycles will be repeated every three weeks up to 6 cycles Bevacizumab monotherapy as maintenance allowed in non-progressive tumors

Drug: gemcitabine, cisplatin and bevacizumab

Interventions

gemcitabine, cisplatin and bevacizumab DRUG

Therapeutic

Also known as: Avastin

gemcitabine, cisplatin and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Give the written informed consent to participate in the trial before carrying out any specific study procedure.
• Histological or cytological non microcytic lung cancer (NMLC) and non squamous advanced locally or metastatic (IIIB/IV) lung cancer confirmation
• Capability to take on the obligations with study protocol requirements.
• Patients 18 years old.
• ECOG functional status 0 or 1.
• At least a measurable lung lesion with conventional TAC (i.e. ≥ 1cm) in at least one dimension its RECIST criteria (v.1.1) which has not been irradiated.
• Appropriate bone marrow function.
• Appropriate hepatic function.
• \. International normalized ratio (INR) ≤ 1.5 and activate partial thromboplastin time (aPTT) ≤ 1.5 x UNL 7 days previous to the first study drug administration, unless patients have been used prophylactic anticoagulant treatment 11. Patients with brain metastasis which had been treated and also asymptomatic , they are eligible to participate in the study.
• \. Female patients cannot be pregnant nor lactating. 13. Male fertile patients have to use a high effective method of contraception.

You may not qualify if:

• Previous treatment with systemic chemotherapy for advance NMLC
• Non microcytic- microcytic mix histology or adeno-squamous mix carcinomas with a predominant squamous component
• Hemoptysis history ≥ grade 2 (defined as at least 2.5 ml of bright red blood) in a period of 3 months prior to receive the study drugs
• Surgery (including open biopsy) or significant traumatic injury in a period of 28 day prior to receive the study drugs.
• Minor surgery including a catheter insertion in a period of 24h prior to the first infusion of bevacizumab
• Proof that the tumor can compress or invade a main vessel in image tests
• Radiotherapy in any site for any reason in a period of 28 days prior to receive the study drugs. It is permitted palliative radiotherapy to bone lesions .
• Aspirin based medication (\> 325 mg/day or clopidogrel \> 75mg/day) present or recent (in a period of 10 days from the first bevacizumab infusion). Medication with oral anticoagulants agents or parenteral medication on full doses (e.g. in a therapeutic range) or the use of thrombolytic agents with present and recent therapeutic intentions (in a period of 10 days prior to the first bevacizumab infusion). The prophylactic medication with anticoagulants is permitted
• History or evidence of inheritance bleeding diathesis or coagulopathy with bleeding risk
• Active gastrointestinal bleeding
• Inadequate controlled hypertension .
• Cardiovascular disease .
• Wounds that do not heal, active peptide ulcer or non treated bone fractures.
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess in the 6 months prior to receive the study drugs
• Known hypersensitivity to bevacizumab, cisplatin or gemcitabine or any of its excipients

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (1)

Hospital Clinic

Barcelona, Barcelona, 08036, Spain

Location

Related Publications (6)

• Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. doi: 10.1056/NEJMoa061884.

  PMID: 17167137 BACKGROUND

• Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009 Mar 10;27(8):1227-34. doi: 10.1200/JCO.2007.14.5466. Epub 2009 Feb 2.

  PMID: 19188680 BACKGROUND

• Tacelli N, Remy-Jardin M, Copin MC, Scherpereel A, Mensier E, Jaillard S, Lafitte JJ, Klotz E, Duhamel A, Remy J. Assessment of non-small cell lung cancer perfusion: pathologic-CT correlation in 15 patients. Radiology. 2010 Dec;257(3):863-71. doi: 10.1148/radiol.10100181. Epub 2010 Sep 15.

  PMID: 20843993 BACKGROUND

• Fraioli F, Vetere S, Anile M, Venuta F. Computed tomography perfusion: a new method to evaluate response to therapy in lung cancer. J Thorac Oncol. 2011 Sep;6(9):1599-600. doi: 10.1097/JTO.0b013e3182259207. No abstract available.

  PMID: 21849856 BACKGROUND

• Tacelli N, Santangelo T, Scherpereel A, Duhamel A, Deken V, Klotz E, Cortot A, Lafitte JJ, Wallyn F, Remy J, Remy-Jardin M. Perfusion CT allows prediction of therapy response in non-small cell lung cancer treated with conventional and anti-angiogenic chemotherapy. Eur Radiol. 2013 Aug;23(8):2127-36. doi: 10.1007/s00330-013-2821-2. Epub 2013 Apr 4.

  PMID: 23553586 BACKGROUND

• Yuan X, Zhang J, Quan C, Cao J, Ao G, Tian Y, Li H. Differentiation of malignant and benign pulmonary nodules with first-pass dual-input perfusion CT. Eur Radiol. 2013 Sep;23(9):2469-74. doi: 10.1007/s00330-013-2842-x. Epub 2013 Jun 22.

  PMID: 23793548 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gemcitabine; Cisplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Noemi Reguart, MD, PhD

  Hospital Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Oncologist

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 12, 2014
• Study Start: July 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 5, 2016

Record last verified: 2016-10

Locations

ES (1)