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

Spanish Lung Cancer Group

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Radiation: Radiotherapy; Drug: Vinorelbine; Drug: Cisplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02709720

2015-003312-21 (EudraCT Number)

GECP 15/02_NORA

Details and patient eligibility

About

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

Full 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.

Enrollment: 68 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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68 participants in 1 patient group

1 Experimental group

Experimental group

Description:

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.

Treatment:

Drug: Cisplatin

Drug: Cisplatin

Drug: Vinorelbine

Radiation: Radiotherapy

Drug: Vinorelbine