NORA: Locally Advanced Trial of Tri-weekly Metronomic Oral Vinorelbine and Cisplatin as Induction Therapy and Subsequent Concomitance With Radiation Therapy in Patients With Unresectable Non Small Cell Lung Cancer (NSCLC)

Sponsor

Spanish Lung Cancer Group (Other)

Overall Status

Completed

CT.gov ID

NCT02709720

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: Vinorelbine Drug: Cisplatin Drug: Vinorelbine Drug: Cisplatin Radiation: Radiotherapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 15, 2016

Actual Primary Completion Date :

Apr 15, 2019

Actual Study Completion Date :

Dec 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 2 cycles of metronomic Vinorelbine 50 mg + cisplatin, followed by 2 cycles of Vinorelbine 30 mg + cisplatin concomitant with radiotherapy	Drug: Vinorelbine Cycle 1 and 2 50 mg/day, (Monday, Wednesday and Friday) Other Names: Navelbine Drug: Cisplatin Cycle 1 and 2 day 1, 80 mg/m2 Drug: Vinorelbine Cycle 3 and 4 30 mg/day, (Monday, Wednesday and Friday) Other Names: Navelbine Drug: Cisplatin Cycle 3 and 4 day 1, 80 mg/m2 Radiation: Radiotherapy concomitant therapy during cycles 3 and 4. Total dose: 66Gy

Arm

Intervention/Treatment

Experimental: 1

2 cycles of metronomic Vinorelbine 50 mg + cisplatin, followed by 2 cycles of Vinorelbine 30 mg + cisplatin concomitant with radiotherapy

Drug: Vinorelbine

Cycle 1 and 2 50 mg/day, (Monday, Wednesday and Friday)

Other Names:

Navelbine

Drug: Cisplatin

Cycle 1 and 2 day 1, 80 mg/m2

Drug: Vinorelbine

Cycle 3 and 4 30 mg/day, (Monday, Wednesday and Friday)

Other Names:

Navelbine

Drug: Cisplatin

Cycle 3 and 4 day 1, 80 mg/m2

Radiation: Radiotherapy

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

Outcome Measures

Primary Outcome Measures

Efficacy (according to progression-free survival of patient) [From patient inclusion up to the date of first documented progression or date of death from any cause, whichever came first, up to 12 months.]
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. 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.

Secondary Outcome Measures

Response Rate [Measured during the first assessment of the patient, up to 6 weeks from the inclusion of the patient]
The objective response rate will be calculated from the sum of the number of patients whose best response is complete response and partial response divided by the total number of patients eligible for the analysis.
Overall Survival [From inclusion in the study to death (estimated period 12 months)]
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.
Number of participants with treatment-related adverse events as assessed by common toxicity criteria (CTCAE) v4.0 [From first drug administration to 30 days after last administration and 90 days after radiotherapy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
2	ICO-Badalona	Badalona	Barcelona	Spain	08916
3	Hospital Provincial de Castellón	Castelló de la Plana	Castelló	Spain	12002
4	H. Son Espases	Palma de Mallorca	Mallorca	Spain	07014
5	Hospital Lluís Alcanyís	Xàtiva	Valencia	Spain	46800
6	Hospital de Basurto	Bilbao	Vizcaya	Spain	48013
7	H.G.U. Alicante	Alicante		Spain	03010
8	Hospital de La Santa Creu I Sant Pau	Barcelona		Spain	08041
9	Hospital de Jaén	Jaén		Spain	23007
10	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
11	H. de la Princesa	Madrid		Spain	28006
12	H.U. Puerta de Hierro	Madrid		Spain	28035
13	Hospital Fundación Jiménez Díaz	Madrid		Spain	28040
14	H. Clínico San Carlos	Madrid		Spain
15	H. Son Llàtzer	Palma de Mallorca		Spain	07198
16	H. de Donostia	San Sebastian		Spain	20014
17	Hospital Virgen de La Macrena	Sevilla		Spain	41009
18	Hospital Clínico Lozano Blesa	Zaragoza		Spain	50009

Sponsors and Collaborators

Spanish Lung Cancer Group

Investigators

Study Chair: Mariano Provencio, MD, Hospital Puerta de Hierro
Principal Investigator: Bartomeu Massutí, MD, Hospital General Universitario de Alicante
Principal Investigator: Teresa Morán, MD, Germans Trias i Pujol Hospital
Principal Investigator: José Luis González Larriba, MD, Hospital San Carlos, Madrid
Principal Investigator: Manuel Dómine, MD, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
Principal Investigator: José Miguel Sánchez, MD, Hospital de la Princesa
Principal Investigator: Ramón de las Peñas, MD, Hospital Provincial de Castellón
Principal Investigator: María Guirado, MD, Hospital Gnral de Elche
Principal Investigator: Dolores Isla, MD, Hospital Lozano Blesa
Principal Investigator: Raquel Marsé, MD, Hospital Son Espases
Principal Investigator: Mª Angeles Sala, MD, Hospital de Basurto
Principal Investigator: Juan Coves, MD, Hospital Son Llátzer
Principal Investigator: Ana Laura Ortega, MD, Hospital de Jaén
Principal Investigator: David Vicente, MD, Hospital Universitario Virgen Macarena
Principal Investigator: Regina Gironés, MD, Hospital LLuís Alcanyís
Principal Investigator: Alfredo Paredes, MD, Hospital de Donostia
Principal Investigator: Margarita Majem, MD, Hospital Sant Pau i de la Santa Creu
Principal Investigator: Sergio Vázquez, MD, Hospital Lucus Agustí