Clinical trial NCT02709720: Study of Vinorelbine and Cisplatin as Induction Therapy With Radiotherapy in Patients With Unresectable NSCLC
Official title: Phase II Clinical Trial With Metronomic Oral Vinorelbine and Tri-weekly Cisplatin as Induction Therapy and Subsequent Concomitantly With Radiotherapy (RT) in Patients With Lung Cancer (NSCLC) Locally Advanced Unresectable
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Lung Cancer
Cancer Lung Disease
NORA
GECP 15/02
Metronomic administration
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2016-03-16
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy and subsequent concomitantly with radiotherapy (RT) in patients with lung cancer (NSCLC) locally advanced unresectable

Detailed description: Hypothesis: At present, administration of concomitant chemotherapy and radiation therapy is considered a treatment of choice for patients with unresectable stage III tumor selected clinically.

There is at present a systemic considered standard treatment in combination with radical radiotherapy. Nor is it established a dose of standard radiation therapy, but it is known that should never be less than 60Gy57.

Vinorelbine has shown a strong radio-sensitizer in-vitro37 effect. In the phase II study, The combination of oral vinorelbine with cisplatin as induction therapy and then concomitantly with radiotherapy (66Gy) has provided very encouraging efficacy results. Recently in the vortex scheme cisplatin study with oral vinorelbine concomitant maintained with radiation from the second cycle of chemotherapy was tested.

It is therefore a priority in this segment pathology seeking treatment regimens that improve the effectiveness and toxicity. Metronomic chemotherapy started with the idea of administering a cytostatic divided doses, for an extended period without interruption, can provide the advantage of exposing patients to significant dose chemotherapy without worsening the toxicity profile. All this makes it an attractive treatment strategy, and can also maintain radio sensitizing effect during concomitance.

Eligibility criteria: Inclusion criteria:

* Patients with histologically confirmed recent non small cell lung cancer unresectable stage IIIA and IIIB.
* Perform a baseline positron emission tomography (PET-CT) to rule out the presence of distant disease and confirm that it is a non-NSCLC radical surgical treatment candidate.
* The positive mediastinal lymph nodes by PET-CT must be confirmed histologically. Mediastinal involvement may be considered without histologically observe when there is a mass of lymph nodes where the margins are not distinguished.
* At least one measurable lesion on computerized tomography (CT).
* Performance status 0-1.
* Life expectancy\> 12 weeks.
* Age ≥18 years and ≤ 75 years.
* Right renal function: creatinine ≤ 1.5 mg / dl or creatinine clearance\> 60 ml / min.
* Right hematologic function: hemoglobin\> 10 g / dl, neutrophils ≥ 1500 / mm3 and platelets ≥ 100,000 / mm3.
* Right hepatic function: bilirubin ≤ 1.5 times the upper limit of each center, transaminases ≤ 2.5 above the normal limit.
* Right lung function without bronchodilators: defined by a forced expiratory volume in 1 second (FEV1)\> 50% of predicted normal volume and lung diffusing capacity for carbon monoxide (DLCO)\> 40% of predicted normal.
* The proportion of normal lung exposed to\> 20 Gy RT (V20) shall be ≤ 35%.This must be fulfilled before the start of treatment cycle 3.
* Signature of informed consent.

Exclusion Criteria:

* Weight loss\> 10% in the 3 months prior to study entry.
* Intestinal problems that do not ensure proper absorption of oral vinorelbine.
* Pregnant or lactating women. Women of childbearing potential should have a negative pregnancy test, and both men and women under this condition should take contraceptive measures throughout the study.
* symptomatic sensory neuropathy\> grade 1 toxicity criteria according to the CTCAE v4.
* Comorbidities uncontrolled.
* syndrome of the superior vena cava.
* pleural or pericardial effusion: are both considered as indicative of metastatic disease unless proven otherwise. Those who still remain cytologically negative for malignancy, are exudates also be excluded. It may include those with pleural effusion visible on chest radiography or too small to perform diagnostic puncture safely.
* Known hypersensitivity to drugs with similar study drug structure.
* Previous treatment with anticancer drugs, previous surgery or thoracic radiotherapy for lung cancer or for other reasons.
* History of other malignancy treated properly within 5 years except carcinoma in situ of the cervix or breast skin and basal cell carcinoma.
* Concomitant treatment with other antineoplastic drug or investigational.
* Patients at any psychological, family, sociological or geographical that may hinder compliance with the study protocol and monitoring program.
* history of neurological or psychiatric disorders that impede a properly understanding of the informed consent.

Primary outcomes:
measure: Progression-free Survival
timeFrame: From patient inclusion up to the date of first documented progression or date of death from any cause, whichever came first, up to 24 months.
Secondary outcomes:
measure: Objective Response Rate 6 Month
timeFrame: From the start of the treatment of the patient to 6 month afther the treatment end
measure: Overall Survival (Estimated)
timeFrame: From the date of randomization until end of follow up or death, up to 24 months.
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Badalona
country: Spain
facility: ICO-Badalona
state: Barcelona
city: Castelló de la Plana
country: Spain
facility: Hospital Provincial de Castellón
state: Castelló
city: Palma de Mallorca
country: Spain
facility: H. Son Espases
state: Mallorca
city: Xàtiva
country: Spain
facility: Hospital Lluís Alcanyís
state: Valencia
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Alicante
country: Spain
facility: H.G.U. Alicante
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Jaén
country: Spain
facility: Hospital de Jaén
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: H. de la Princesa
city: Madrid
country: Spain
facility: H.U. Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: H. Clínico San Carlos
city: Palma de Mallorca
country: Spain
facility: H. Son Llàtzer
city: San Sebastian
country: Spain
facility: H. de Donostia
city: Sevilla
country: Spain
facility: Hospital Virgen de La Macrena
city: Zaragoza
country: Spain
facility: Hospital Clínico Lozano Blesa
Study officials:
affiliation: Hospital Puerta de Hierro
name: Mariano Provencio, MD
role: STUDY_CHAIR
affiliation: Hospital General Universitario de Alicante
name: Bartomeu Massutí, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germans Trias i Pujol Hospital
name: Teresa Morán, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital San Carlos, Madrid
name: José Luis González Larriba, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
name: Manuel Dómine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
name: José Miguel Sánchez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Provincial de Castellón
name: Ramón de las Peñas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Gnral de Elche
name: María Guirado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Lozano Blesa
name: Dolores Isla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Son Espases
name: Raquel Marsé, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Basurto
name: Mª Angeles Sala, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Son Llátzer
name: Juan Coves, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Jaén
name: Ana Laura Ortega, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Virgen Macarena
name: David Vicente, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital LLuís Alcanyís
name: Regina Gironés, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Donostia
name: Alfredo Paredes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Sant Pau i de la Santa Creu
name: Margarita Majem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Lucus Agustí
name: Sergio Vázquez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Provencio M, Majem M, Guirado M, Massuti B, de Las Penas R, Ortega AL, Domine M, Marse R, Sala MA, Paredes A, Moran T, Vazquez S, Coves J, Larriba JLG, Sanchez JM, Vicente D, Farre N, Fornos LF, Zapata I, Franco F, Serna-Blasco R, Romero A, Isla D. Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection. Lung Cancer. 2021 Mar;153:25-34. doi: 10.1016/j.lungcan.2021.01.005. Epub 2021 Jan 10.