Study of Vinorelbine and Cisplatin as Induction Therapy With Radiotherapy in Patients With Unresectable NSCLC

Lung Cancer Clinical Trial

— NORA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02709720
• Other study ID #: GECP 15/02_NORA
• Secondary ID: 2015-003312-21
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2016
• Est. completion date: December 16, 2019

Study information

• Verified date: April 2023
• Source: Spanish Lung Cancer Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: December 16, 2019
• Est. primary completion date: April 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• Vinorelbine
Cycle 1 and 2 50 mg/day, (Monday, Wednesday and Friday)
• Cisplatin
Cycle 1 and 2 day 1, 80 mg/m2
• Vinorelbine
Cycle 3 and 4 30 mg/day, (Monday, Wednesday and Friday)
• Cisplatin
Cycle 3 and 4 day 1, 80 mg/m2

Radiation:
• Radiotherapy
concomitant therapy during cycles 3 and 4. Total dose: 66Gy

Locations

Country	Name	City	State
Spain	H.G.U. Alicante	Alicante
Spain	ICO-Badalona	Badalona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	Barcelona
Spain	Hospital de Basurto	Bilbao	Vizcaya
Spain	Hospital Provincial de Castellón	Castelló de la Plana	Castelló
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital de Jaén	Jaén
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	H. Clínico San Carlos	Madrid
Spain	H. de la Princesa	Madrid
Spain	H.U. Puerta de Hierro	Madrid
Spain	Hospital Fundación Jiménez Díaz	Madrid
Spain	H. Son Espases	Palma de Mallorca	Mallorca
Spain	H. Son Llàtzer	Palma de Mallorca
Spain	H. de Donostia	San Sebastian
Spain	Hospital Virgen de La Macrena	Sevilla
Spain	Hospital Lluís Alcanyís	Xàtiva	Valencia
Spain	Hospital Clínico Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Lung Cancer Group

Country where clinical trial is conducted

Spain, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	To evaluate the efficacy in terms of progression-free survival (PFS) of oral metronomical vinorelbine and cisplatin as an induction treatment and then with concomitant radiotherapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions The PFS is defined as the time from the moment of patient inclusion to the documentation of progression or death from any cause (patients who die without evidence of progression, will be considered events on the date of death).	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	Objective Response Rate 6 Month	The objective response rate will be calculated from the sum of the number of patients whose best response is complete response, partial response and stable disease divided by the total number of patients eligible for the analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.	From the start of the treatment of the patient to 6 month afther the treatment end
Secondary	Overall Survival (Estimated)	Overall survival will be measured from the date of patient inclusion until death or loss of follow-up. In patients who have not died, the duration of survival will be censored on the date of the last contact if the patient causes loss of follow-up or on the date of the latest news.	From the date of randomization until end of follow up or death, up to 24 months.

External Links

•   Web page of the sponsor where users can find more information about Fundación GECP studies