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

NCT ID: NCT02709720

Last Updated: 2024-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-15
• Study Completion Date: 2019-12-16

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 Experimental group

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

Induction chemotherapy:

• Cisplatin: 80 mg/m2 day 1 every 21 days, for 2 cycles.
• Metronomic oral vinorelbine: 50mg/day, 3 days of each week for 2 cycles.

Concomitant chemotherapy and radiotherapy:

• Cisplatin: 80 mg/m2 day 1 every 21 days, for 2 cycles.
• Metronomic oral vinorelbine: 30mg/day, 3 days of each week for 2 cycles. 1 cycle equals 21 days

Radiotherapy treatment:

Patients will receive concomitant thoracic radiation therapy, using a technique three-dimensional conformal radiation therapy, using an accelerator linear that operates with energy rays ≥ 6 MV. The total target RTT dose will be 66 Gy in 33 daily fractions of 2 Gy, which will be prescribed in accordance with the document of ICRU reference 50 of ICRU.

Group Type: EXPERIMENTAL

Vinorelbine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Cycle 1 and 2 day 1, 80 mg/m2

Vinorelbine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

Cycle 3 and 4 day 1, 80 mg/m2

Radiotherapy

Intervention Type: RADIATION

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

Interventions

Vinorelbine

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

Intervention Type: DRUG

Cisplatin

Cycle 1 and 2 day 1, 80 mg/m2

Intervention Type: DRUG

Vinorelbine

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

Intervention Type: DRUG

Cisplatin

Cycle 3 and 4 day 1, 80 mg/m2

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Other Intervention Names

Navelbine; Navelbine

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Lung Cancer Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mariano Provencio, MD

Role: STUDY_CHAIR

Hospital Puerta de Hierro

Bartomeu Massutí, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General Universitario de Alicante

Teresa Morán, MD

Role: PRINCIPAL_INVESTIGATOR

Germans Trias i Pujol Hospital

José Luis González Larriba, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital San Carlos, Madrid

Manuel Dómine, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

José Miguel Sánchez, MD

Role: PRINCIPAL_INVESTIGATOR

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Ramón de las Peñas, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Provincial de Castellón

María Guirado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Gnral de Elche

Dolores Isla, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Lozano Blesa

Raquel Marsé, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Espases

Mª Angeles Sala, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Basurto

Juan Coves, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Son Llátzer

Ana Laura Ortega, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Jaén

David Vicente, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Virgen Macarena

Regina Gironés, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital LLuís Alcanyís

Alfredo Paredes, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital de Donostia

Margarita Majem, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Sant Pau i de la Santa Creu

Sergio Vázquez, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Lucus Agustí

Locations

Hospital General Universitario de Elche

Elche, Alicante, Spain

ICO-Badalona

Badalona, Barcelona, Spain

Hospital Provincial de Castellón

Castellon, Castelló, Spain

H. Son Espases

Palma de Mallorca, Mallorca, Spain

Hospital Lluís Alcanyís

Xàtiva, Valencia, Spain

Hospital de Basurto

Bilbao, Vizcaya, Spain

H.G.U. Alicante

Alicante, , Spain

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

H. de Donostia

Donostia / San Sebastian, , Spain

Hospital de Jaén

Jaén, , Spain

Hospital Universitario Lucus Augusti

Lugo, , Spain

H. de la Princesa

Madrid, , Spain

H.U. Puerta de Hierro

Madrid, , Spain

Hospital Fundación Jiménez Díaz

Madrid, , Spain

H. Clínico San Carlos

Madrid, , Spain

H. Son Llàtzer

Palma de Mallorca, , Spain

Hospital Virgen de La Macrena

Seville, , Spain

Hospital Clínico Lozano Blesa

Zaragoza, , Spain

Countries

Spain

References

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.

Reference Type: RESULT

PMID: 33453470 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.gecp.org

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

Other Identifiers

2015-003312-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GECP 15/02_NORA

Identifier Type: -

Identifier Source: org_study_id