Lung Cancer
Conditions
Keywords
Lung Cancer, Cancer Lung Disease, NORA, GECP 15/02, Metronomic administration
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.
Interventions
DRUGVinorelbine
Cycle 1 and 2 50 mg/day, (Monday, Wednesday and Friday)
DRUGCisplatin
Cycle 1 and 2 day 1, 80 mg/m2
RADIATIONRadiotherapy
concomitant therapy during cycles 3 and 4. Total dose: 66Gy
Sponsors
Spanish Lung Cancer Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate 6 Month | From the start of the treatment of the patient to 6 month afther the treatment end | 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. |
| Overall Survival (Estimated) | From the date of randomization until end of follow up or death, up to 24 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. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Group 2 cycles of metronomic Vinorelbine 50 mg + cisplatin, followed by 2 cycles of Vinorelbine 30 mg + cisplatin concomitant with radiotherapy
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
Radiotherapy: concomitant therapy during cycles 3 and 4. Total dose: 66Gy | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Non-compliance with inclusion criteria | 1 |
| Overall Study | Not take study medication | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Experimental Group |
|---|---|
| Age, Continuous | 62 years |
| Body mass index | 26.6 kg/m^2 |
| Compliance Treatment completed | 51 participants |
| Compliance Treatment not completed | 14 participants |
| Cycles C1 completed and C2 incompleted | 1 Participants |
| Cycles Cycle 1 and Cycle 2 completed | 6 Participants |
| Cycles Cycle1 and Cycle 2 completed and C3 incompleted | 1 Participants |
| Cycles Cycle 1 completed | 2 Participants |
| Cycles Cycle 1 incompleted | 2 Participants |
| Cycles Cycle 1 to Cycle 3 completed | 2 Participants |
| Cycles Cycle 1 to Cycle 4 completed | 51 Participants |
| ECOG ECOG 0 | 34 Participants |
| ECOG ECOG 1 | 31 Participants |
| Electrocardiogram Normal | 54 participants |
| Electrocardiogram Not done | 2 participants |
| Electrocardiogram Not normal | 9 participants |
| Histology Adenocarcinoma | 29 Participants |
| Histology Adenosquamous carcinoma | 4 Participants |
| Histology Large cell carcinoma | 1 Participants |
| Histology Not registered | 2 Participants |
| Histology Others | 2 Participants |
| Histology Squamous cell carcinoma | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 65 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Spain | 65 Participants |
| Respiratory functional tests Normal | 64 participants |
| Respiratory functional tests Not normal | 1 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 50 Participants |
| Smoking status Former smoker | 27 Participants |
| Smoking status Non smoker | 3 Participants |
| Smoking status Smoker | 35 Participants |
| Stage IIIA | 27 participants |
| Stage IIIB | 38 participants |
| Stage M M0 | 65 Participants |
| Stage M M1 | 0 Participants |
| Stage N N0 | 5 Participants |
| Stage N N1 | 7 Participants |
| Stage N N2 | 35 Participants |
| Stage N N3 | 18 Participants |
| Stage T T1 | 5 Participants |
| Stage T T2 | 10 Participants |
| Stage T T3 | 13 Participants |
| Stage T T4 | 36 Participants |
| Stage T TX | 1 Participants |
| Weight Normal weight | 21 Participants |
| Weight Obesity | 17 Participants |
| Weight Overweight | 25 Participants |
| Weight Under weight | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 65 |
| other Total, other adverse events | 64 / 65 |
| serious Total, serious adverse events | 10 / 65 |
Outcome results
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).
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 24 months.
Population: All study patients will be included and analysed in the intention-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group | Progression-free Survival | 11.5 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.
Time frame: From the start of the treatment of the patient to 6 month afther the treatment end
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Group | Objective Response Rate 6 Month | 78.1 percentage of participants |
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.
Time frame: From the date of randomization until end of follow up or death, up to 24 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Group | Overall Survival (Estimated) | 35.6 Month |