Back to results

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) (NORA)

Primary Purpose

Lung Cancer

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Vinorelbine

Cisplatin

Vinorelbine

Cisplatin

Radiotherapy

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Lung Cancer, Cancer Lung Disease, NORA, GECP 15/02, Metronomic administration

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

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

Outcomes

Primary Outcome Measures

Efficacy (according to progression-free survival of patient)

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

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

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

Full Information

NCT ID

NCT02709720

First Posted

February 2, 2016

Last Updated

January 8, 2020

Sponsor

Spanish Lung Cancer Group

1. Study Identification

Unique Protocol Identification Number

NCT02709720

Brief Title

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)

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

April 15, 2016 (Actual)

Primary Completion Date

April 15, 2019 (Actual)

Study Completion Date

December 16, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Spanish Lung Cancer Group

4. Oversight

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer

Keywords

Lung Cancer, Cancer Lung Disease, NORA, GECP 15/02, Metronomic administration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

67 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Vinorelbine

Other Intervention Name(s)

Navelbine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cycle 1 and 2 day 1, 80 mg/m2

Intervention Type

Drug

Intervention Name(s)

Vinorelbine

Other Intervention Name(s)

Navelbine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Intervention Description

Cycle 3 and 4 day 1, 80 mg/m2

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

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

Primary Outcome Measure Information:

Title

Efficacy (according to progression-free survival of patient)

Description

Time Frame

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.

Secondary Outcome Measure Information:

Title

Response Rate

Description

Time Frame

Measured during the first assessment of the patient, up to 6 weeks from the inclusion of the patient

Title

Overall Survival

Description

Time Frame

From inclusion in the study to death (estimated period 12 months)

Title

Number of participants with treatment-related adverse events as assessed by common toxicity criteria (CTCAE) v4.0

Time Frame

From first drug administration to 30 days after last administration and 90 days after radiotherapy

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: