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NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed

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ClinicalTrials.gov Identifier: NCT01098266
Recruitment Status : Completed
First Posted : April 2, 2010
Results First Posted : September 17, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Malignant Pleural Mesothelioma
Interventions Drug: NGR-hTNF plus Best Investigator's Choice (BIC)
Drug: Placebo plus Best Investigator's Choice (BIC)
Enrollment 400
Recruitment Details Study Period: April 12th, 2010(First enrolment); January 21st, 2013 (date of last enrolment); April 29th, 2014 (cut-off date). 15 clinical sites in Italy, 10 in UK, 7 in USA, 4 in Belgium, 2 in Canada, 2 in Netherland, 2 in Poland, 1 in Egypt, 1 in Ireland;1 in Sweden
Pre-assignment Details Before randomization, the physician had to decide for each patient if he/she was candidate to either Best Supportive Care (BSC) alone or combined with single-agent chemotherapy.
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Period Title: Overall Study
Started 200 200
Completed 193 193
Not Completed 7 7
Reason Not Completed
Physician Decision             1             0
Death             3             2
Withdrawal by Subject             3             5
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC Total
Hide Arm/Group Description

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Total of all reporting groups
Overall Number of Baseline Participants 200 200 400
Hide Baseline Analysis Population Description
Patients ≥ 18 years with advanced malignant pleural mesothelioma previously treated with a pemetrexed based chemotherapy regimen for advanced or metastatic disease.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 200 participants 200 participants 400 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
92
  46.0%
87
  43.5%
179
  44.8%
>=65 years
108
  54.0%
113
  56.5%
221
  55.3%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 200 participants 200 participants 400 participants
65
(25 to 89)
67
(31 to 81)
66
(25 to 89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 200 participants 200 participants 400 participants
Female
44
  22.0%
55
  27.5%
99
  24.8%
Male
156
  78.0%
145
  72.5%
301
  75.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 200 participants 200 participants 400 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   0.5%
1
   0.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   1.0%
0
   0.0%
2
   0.5%
White
198
  99.0%
197
  98.5%
395
  98.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
2
   1.0%
2
   0.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 200 participants 200 participants 400 participants
Canada 3 5 8
Netherlands 5 2 7
Sweden 1 1 2
Belgium 5 8 13
United States 14 12 26
Ireland 3 1 4
Egypt 17 19 36
Poland 17 14 31
Italy 79 84 163
United Kingdom 49 46 95
France 4 6 10
Spain 3 2 5
1.Primary Outcome
Title Overall Survival (OS)
Hide Description Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive
Time Frame From date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assesed up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 200 200
Median (95% Confidence Interval)
Unit of Measure: months
8.5
(7.2 to 9.9)
8.0
(6.6 to 8.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: NGR-hTNF + BIC, B: Placebo+BIC
Comments Study with one control per experimental patient, an accrual interval of 24 months, and an additional FU after the accrual interval of 12 months.If the true HR of experimental relative to control patients was 0.726, then 195 experimental patients and 195 control patients were required to be able to reject the null hypothesis that the experimental and control survival curves were equal with probability (power)0.80 Type I error probability associated with this test of this null hypothesis was 0.05
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments The log-rank test (unstratified) was used to compare the two treatment arms. In addition, a stratified version of the log-rank test was performed with the stratification factors used for randomization.
Method Log Rank
Comments Cox regression analyses (unstratified and stratified) were performed to assess the influence of baseline covariates in an exploratory manner.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.75 to 1.18
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description Defined as the time from the date of randomization until disease progression, or deathdue to any couse or the last patient was konwn to be alive. Progression is defined usind Response Evaluation Criteria In Solid Tumors Criteria (Recist v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition torelative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm. In addition the appearance of one or more new lesions was also considered progression
Time Frame From the date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assessed up to 48 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 200 200
Median (95% Confidence Interval)
Unit of Measure: months
3.4
(2.7 to 4.1)
3.0
(2.3 to 3.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: NGR-hTNF + BIC, B: Placebo+BIC
Comments The log-rank test (unstratified and stratified) was used at an alpha level of 5% to test for differences in PFS between the two treatment arms. Kaplan-Meier curves and estimates were provided.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.65
Comments [Not Specified]
Method Log Rank
Comments Cox regression analyses (unstratified and stratified) was performed to assess the influence of baseline covariates in an exploratory manner.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.78 to 1.17
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description Disease control rate (DCR), defined as the percentage of patients who have a best-response rating of complete or partial response or stable disease, according to MPM-modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Time Frame Assessed every 6-12 weeks, up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 200 200
Measure Type: Count of Participants
Unit of Measure: Participants
Disease control rate (DCR)
114
  57.0%
109
  54.5%
Complete or partial response (CR o PR)
3
   1.5%
6
   3.0%
Stable disease (SD)
111
  55.5%
103
  51.5%
Progressive disease (PD)
51
  25.5%
71
  35.5%
Nonassessable (NA)
35
  17.5%
20
  10.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: NGR-hTNF + BIC, B: Placebo+BIC
Comments Difference in DCR between the two treatment arms were tested using a chi-squared test with 95% confidence intervals calculated in each treatment arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.62
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.76 to 1.68
Estimation Comments Logistic regression analyses were performed to assess the influence of baseline covariates in an exploratory manner
4.Secondary Outcome
Title Number of Partecipants With Disease Control for ≥ 6 Months
Hide Description Measured from the date of randomization until disease progression, or death due to any cause
Time Frame Assessed every 6-12 weeks, up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Duration of disease control ≥ 6 months
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 200 200
Measure Type: Count of Participants
Unit of Measure: Participants
84
  42.0%
76
  38.0%
5.Secondary Outcome
Title Number of Partecipants With Adverse Events
Hide Description All adverse events will be recorded according to CTC version 4.02 (CTC reference: http://ctep.cancer.gov/reporting/ctc.html) on the case report forms (CRFs); the investigator will decide if those events are drug related and his decision will be recorded on the forms for all adverse events.
Time Frame Assessed every 6-12 weeks, up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The safety data referred to patients of both arms who received at least one treatment and is termed as safety population (n=386)
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 193 193
Measure Type: Number
Unit of Measure: participants
Study-emergent AEs of any grade 191 185
Study-emergent AEs of grade 3 102 86
Study-emergent AEs of grade 4 22 19
Study-emergent AEs of grade 5 12 13
Treatment-related AEs of grade 5 0 0
Treatment discontinuation due to AEs 31 24
6.Secondary Outcome
Title Time to LCSS Symptomatic Progression
Hide Description Quality of life (QoL) assessment was performed by using a questionnaire according to The Lung Cancer Symptom Scale (LCSS) . The LCSS is designed as a disease and site-specific measure of QoL particularly for use in clinical trials. It evaluates six major symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain) associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global QoL. Within this trial the questionnaire according to LCSS was only recorded by the patient (patient’s scale). QoL assessment was performed by using a questionnaire according to LCSS, which consists of nine 100-mm visual analog scales, with scores reported from 0 to 100 (0 representing the best score). The LCSS subscore is the average symptom burden index computed as the mean score for all six major symptoms. Symptomatic progression was defined as a worsening in the average symptom burden index by 25%.
Time Frame from the date of randomization to the date of the LCSS assessment on which symptomatic progression was identified, assessed on cycle 2, cycle 4 and cycle 6 (each cycle lasted 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a worsening in the average symptom burden index by 25%.
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 175 185
Median (95% Confidence Interval)
Unit of Measure: months
3.2
(2.1 to 4.4)
3.0
(2.8 to 3.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A: NGR-hTNF + BIC, B: Placebo+BIC
Comments QoL assessment was performed by using a questionnaire according to LCSS, which consists of nine 100-mm visual analog scales, with scores reported from 0 to 100(the best score). The LCSS subscore is the average symptom burden index computed as the mean score for all 6 major symptoms. Symptomatic progression was defined as a worsening in the average symptom burden index by 25%.
Type of Statistical Test Other
Comments Two-sided log-rank test was used to compare time to symptomatic progression between treatment arms. Median and 95% confidence limits for the time to symptomatic progression were estimated using Kaplan-Meier survival methodology. Estimates of the treatment effect were expressed as hazard ratio including 95% confidence intervals.
Statistical Test of Hypothesis P-Value 0.5806
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.68 to 1.26
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Evaluation of Medical Care Utilization in the Two Treatment Arms
Hide Description Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters.
Time Frame Assessed every 6-12 weeks, up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description:

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Overall Number of Participants Analyzed 200 200
Measure Type: Count of Participants
Unit of Measure: Participants
ACE INHIBITORS, COMBINATIONS
0
   0.0%
2
   1.0%
ACE INHIBITORS, PLAIN
5
   2.5%
2
   1.0%
ADRENERGICS, INHALANTS
7
   3.5%
10
   5.0%
AMINOGLYCOSIDE ANTIBACTERIALS
2
   1.0%
2
   1.0%
ANESTHETICS, LOCAL
0
   0.0%
4
   2.0%
ANGIOTENSIN II ANTAGONISTS,COMBINATIONS
1
   0.5%
4
   2.0%
ANGIOTENSIN II ANTAGONISTS, plain
2
   1.0%
5
   2.5%
ANTACIDS
7
   3.5%
3
   1.5%
ANTERIOR PITUITARY LOBE HORMONES AND ANALOGUES
13
   6.5%
7
   3.5%
ANTIADRENERGIC AGENTS CENTRALLY ACTING
0
   0.0%
2
   1.0%
ANTIADRENERGIC AGENTS PERIPHERALLY ACTING
0
   0.0%
2
   1.0%
ANTIANDROGENS
0
   0.0%
1
   0.5%
ANTIARRHYTHMICS, CLASS I AND III
4
   2.0%
3
   1.5%
ANTIBIOTICS FOR TOPICAL USE
0
   0.0%
4
   2.0%
ANTIDEPRESSANTS
17
   8.5%
2
   1.0%
ANTIDIARRHEAL MICROORGANISMS
2
   1.0%
1
   0.5%
ANTIEMETICS AND ANTINAUSEANTS
107
  53.5%
110
  55.0%
ANTIEPILEPTICS
3
   1.5%
2
   1.0%
ANTIFIBRINOLYTICS
1
   0.5%
0
   0.0%
ANTIFUNGALS FOR TOPICAL USE
2
   1.0%
0
   0.0%
ANTIGLAUCOMA PREPARATIONS AND MIOTICS
0
   0.0%
1
   0.5%
ANTIGOUT PREPARATIONS
10
   5.0%
12
   6.0%
ANTIHISTAMINES FOR SYSTEMIC USE
66
  33.0%
31
  15.5%
ANTIINFECTIVES
0
   0.0%
1
   0.5%
ANTIINFLAMMATORY AGENTS AND ANTIINFECTIVES IN COM
0
   0.0%
2
   1.0%
ANTIINFLAMMATORY ANANTIRHEUMATIC PRODUCTSD
58
  29.0%
65
  32.5%
ANTIMETABOLITES
1
   0.5%
1
   0.5%
ANTIMYCOTICS FOR SYSTEMIC USE
15
   7.5%
14
   7.0%
ANTIPROPULSIVES
4
   2.0%
8
   4.0%
ANTIPRURITICS
3
   1.5%
2
   1.0%
ANTIPSYCHOTICS
7
   3.5%
3
   1.5%
ANTITHROMBOTIC AGENTS
41
  20.5%
42
  21.0%
ANTIVERTIGO PREPARATIONS
2
   1.0%
1
   0.5%
ANXIOLYTICS
24
  12.0%
16
   8.0%
ASCORBIC ACID (VITAMIN C)
0
   0.0%
1
   0.5%
BACTERIAL VACCINES
1
   0.5%
0
   0.0%
BELLADONNA AND DERIVATIVES
3
   1.5%
4
   2.0%
BETA BLOCKING AGENTS AND OTHER ANTIHYPERTENSIVES
11
   5.5%
15
   7.5%
BETA-LACTAM ANTIBACTERIALS, PENICILLINS
38
  19.0%
29
  14.5%
BILE THERAPY
1
   0.5%
1
   0.5%
BLOOD AND RELATED PRODUCTS
21
  10.5%
26
  13.0%
BLOOD GLUCOSE LOWERING DRUGS EXCL. INSULINS
2
   1.0%
6
   3.0%
CALCIUM
19
   9.5%
12
   6.0%
CAPILLARY STABILIZING
1
   0.5%
0
   0.0%
CARDIAC GLYCOSIDES
1
   0.5%
3
   1.5%
CARDIAC STIMULANTS EXCL CARDIAC GLYCOSIDES
1
   0.5%
0
   0.0%
CORTICOSTEROIDS FOR SYSTEMIC USE, PLAIN
138
  69.0%
108
  54.0%
CORTICOSTEROIDS, PLAIN
2
   1.0%
1
   0.5%
COUGH SUPPRESSANTS AND EXPECTORANTS, COMBINATIONS
2
   1.0%
5
   2.5%
COUGH SUPPRESSANTS, EXCL. COMBINATIONS WITH EXPEC
7
   3.5%
17
   8.5%
DECONGESTANTS AND ANTIALLERGICS
0
   0.0%
1
   0.5%
DIRECT ACTING ANTIVIRALS
2
   1.0%
2
   1.0%
DIURETICS AND POTASSIUM-SPARING AGENTS
6
   3.0%
3
   1.5%
DRUGS AFFECTING BONE
2
   1.0%
3
   1.5%
DRUGS FOR CONSTIPATION
39
  19.5%
63
  31.5%
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS
3
   1.5%
5
   2.5%
DRUGS FOR PEPTIC ULCER AND GASTRO-OESOPHAGEAL REF
74
  37.0%
71
  35.5%
DRUGS FOR TREATMENT OF TUBERCULOSIS
2
   1.0%
0
   0.0%
DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
4
   2.0%
1
   0.5%
ECTOPARASITICIDES, INC SCABICIDESL.
0
   0.0%
1
   0.5%
EMOLLIENTS AND PROTECTIVES
1
   0.5%
0
   0.0%
EXPECTORANTS EXCL COMBINATIONS WITH COUGH SUPPR.
14
   7.0%
9
   4.5%
HIGH-CEILING DIURETICS
19
   9.5%
20
  10.0%
HORMONES AND RELATED AGENTS
0
   0.0%
1
   0.5%
HYPNOTICS AND SEDATIVES
14
   7.0%
14
   7.0%
HYPOTHALAMIC HORMONES
0
   0.0%
1
   0.5%
I.V. SOLUTION ADDITIVES
17
   8.5%
21
  10.5%
I.V. SOLUTIONS
6
   3.0%
10
   5.0%
IMMUNOSTIMULANTS
20
  10.0%
19
   9.5%
INSULINS AND ANALOGUES
5
   2.5%
0
   0.0%
INTESTINAL ANTIINFECTIVES
3
   1.5%
2
   1.0%
IRON PREPARATIONS
14
   7.0%
9
   4.5%
LIPID MODIFYING AGENTS, PLAIN
4
   2.0%
4
   2.0%
LOW-CEILING DIURETICS, EXCL THIAZIDES
1
   0.5%
0
   0.0%
MACROLIDES, LINCOSAMIDES AND STREPTOGRAMINS
8
   4.0%
14
   7.0%
MULTIVITAMINS, COMBINATIONS
1
   0.5%
4
   2.0%
MULTIVITAMINS, PLAIN
4
   2.0%
5
   2.5%
MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
0
   0.0%
1
   0.5%
MYDRIATICS AND CYCLOPLEGICS
2
   1.0%
3
   1.5%
OPIOIDS
135
  67.5%
160
  80.0%
OTHER ANALGESICS AND ANTIPYRETICSD
105
  52.5%
93
  46.5%
OTHER ANTIANEMIC PREPARATIONS
20
  10.0%
20
  10.0%
OTHER ANTIBACTERIALS
4
   2.0%
5
   2.5%
OTHER ANTIDIARRHEALS
1
   0.5%
0
   0.0%
OTHER ANTINEOPLASTIC AGENTS
0
   0.0%
2
   1.0%
OTHER BETA-LACTAM ANTIBACTERIALS
8
   4.0%
9
   4.5%
OTHER CARDIAC PREPARATIONS
3
   1.5%
0
   0.0%
OTHER DRUGS FOR ACID RELATED DISORDERS
0
   0.0%
1
   0.5%
OTHER DRUGS FOR OBSTRUCTIVE
7
   3.5%
8
   4.0%
OTHER MINERAL SUPPLEMENTS
4
   2.0%
5
   2.5%
OTHER NUTRIENTS
4
   2.0%
7
   3.5%
OTHER OPHTHALMOLOGICALS
0
   0.0%
1
   0.5%
OTHER PLAIN VITAMIN PREPARATIONS
2
   1.0%
0
   0.0%
OTHER RESPIRATORY SYSTEM PRODUCTS
2
   1.0%
0
   0.0%
OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEA
3
   1.5%
1
   0.5%
OTHER VITAMIN PRODUCTS, COMBINATIONS
1
   0.5%
2
   1.0%
PERIPHERAL VASODILATORS
0
   0.0%
1
   0.5%
POTASSIUM
4
   2.0%
5
   2.5%
POTASSIUM-SPARING AGENTS
1
   0.5%
5
   2.5%
PROPULSIVES
68
  34.0%
87
  43.5%
PSYCHOLEPTICS AND PSYCHOANALEPTICS
0
   0.0%
1
   0.5%
PSYCHOSTIMULANTS,
0
   0.0%
1
   0.5%
QUINOLONE ANTIBACTERIALS
31
  15.5%
36
  18.0%
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VA
1
   0.5%
6
   3.0%
STOMATOLOGICAL PREPARATIONS
20
  10.0%
19
   9.5%
SULFONAMIDES AND TRIMETHOPRIM
2
   1.0%
0
   0.0%
TETRACYCLINES
0
   0.0%
4
   2.0%
THYROID PREPARATIONS
2
   1.0%
0
   0.0%
TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
1
   0.5%
2
   1.0%
UROLOGICALS
3
   1.5%
1
   0.5%
VASODILATORS USED IN CARDIAC DISEASES
0
   0.0%
2
   1.0%
VIRAL VACCINES
1
   0.5%
0
   0.0%
VITAMIN A AND D
0
   0.0%
5
   2.5%
VITAMIN B1, PLAIN AND IN COMBINATION WITH VITAMIN
0
   0.0%
3
   1.5%
VITAMIN B12 AND FOLIC ACID
7
   3.5%
11
   5.5%
VITAMIN K AND OTHER HEMOSTATICS
1
   0.5%
3
   1.5%
SELECTIVE CALCIUM CHANNEL BLOCKERS WITH DIRECT CA
3
   1.5%
4
   2.0%
Time Frame Through study completation, an average of 2 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title A: NGR-hTNF + BIC B: Placebo+BIC
Hide Arm/Group Description

NGR-hTNF plus Best Investigator's Choice

NGR-hTNF plus Best Investigator's Choice (BIC): - NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo plus Best Investigator's Choice

Placebo plus Best Investigator's Choice (BIC): - Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs.

  • Best Supportive Care: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis
  • Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination:

    1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
    2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
    3. Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
All-Cause Mortality
A: NGR-hTNF + BIC B: Placebo+BIC
Affected / at Risk (%) Affected / at Risk (%)
Total   12/193 (6.22%)      13/193 (6.74%)    
Show Serious Adverse Events Hide Serious Adverse Events
A: NGR-hTNF + BIC B: Placebo+BIC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   56/193 (29.02%)      54/193 (27.98%)    
Blood and lymphatic system disorders     
Neutropenia  1  2/193 (1.04%)  3 4/193 (2.07%)  5
Thrombocytopenia  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Leukopenia  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Neutropenic fever  1  0/193 (0.00%)  0 2/193 (1.04%)  2
Anaemia  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Cardiac disorders     
Pericardial effusion  1  1/193 (0.52%)  1 2/193 (1.04%)  2
Atrial fibrillation  1  1/193 (0.52%)  1 1/193 (0.52%)  1
Cardiac disorder  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Cardiac failure  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Myocardial infarction  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Pericarditis  1  0/193 (0.00%)  1/193 (0.52%) 
Cardiac arresr  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Gastrointestinal disorders     
Intestinal obstruction  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Diarrhoea  1  2/193 (1.04%)  2 0/193 (0.00%)  0
Pancreatitis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Constipation  1  2/193 (1.04%)  2 1/193 (0.52%)  1
Abdominal pain  1  0/193 (0.00%)  0 2/193 (1.04%)  2
Abdominal ascites  1  1/193 (0.52%)  1 1/193 (0.52%)  1
Dysphagia  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Vomiting  1  2/193 (1.04%)  0/193 (0.00%) 
General disorders     
Chills  1  2/193 (1.04%)  2 0/193 (0.00%)  0
Mucositis  1  0/193 (0.00%)  1/193 (0.52%) 
Pyrexia  1  2/193 (1.04%)  2 2/193 (1.04%)  2
Death  1  3/193 (1.55%)  3 2/193 (1.04%)  2
Hyperpyrexia  1  1/193 (0.52%)  0/193 (0.00%) 
Ischaemic ulcer to left heel  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Chest pain  1  3/193 (1.55%)  3 3/193 (1.55%)  3
Deterioration of clinical status  1  1/193 (0.52%)  1 1/193 (0.52%)  1
Admitted for pain control  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Fatigue  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Condition aggraveted  1  4/193 (2.07%)  4 5/193 (2.59%)  5
Hepatobiliary disorders     
Acute hepatitis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Immune system disorders     
Brain mets  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Infections and infestations     
Cellulitis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Pneumonia  1  0/193 (0.00%)  0 3/193 (1.55%)  3
Neutropenic sepsis  1  1/193 (0.52%)  1 1/193 (0.52%)  1
Appendiceal abscess  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Sepsis  1  2/193 (1.04%)  2 1/193 (0.52%)  1
Infection - source unknown  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Viral gastroenteritis  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Lower Respiratory Tract Infection  1  2/193 (1.04%)  2 1/193 (0.52%)  1
Lung Infection  1  0/193 (0.00%)  0 1/193 (0.52%)  1
. Respiratory Tract Infection  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Injury, poisoning and procedural complications     
Uncertain study medication dose delivered  1  4/193 (2.07%)  4 9/193 (4.66%)  9
Drug infusion reaction  1  2/193 (1.04%)  2 0/193 (0.00%)  0
Overdose  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Humerus fracture  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Hip fracture  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Occipital trauma  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Cachexia  1  1/193 (0.52%)  1 1/193 (0.52%)  1
Pleural Mesothelioma  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain right chest wall + right shoulder  1  0/193 (0.00%)  1/193 (0.52%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Paraneoplastic fever  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Brain mets  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Nervous system disorders     
Transient ischaemic attack  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Superior sagittal sinus thrombosis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Right hemispheric cerebrovascular accident  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Encephalopathy  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Jacksonian seizure  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Renal and urinary disorders     
Abnormal renal function  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  2/193 (1.04%)  2 2/193 (1.04%)  2
Dyspnoea  1  4/193 (2.07%)  7 1/193 (0.52%)  1
Respiratory failure  1  2/193 (1.04%)  2 2/193 (1.04%)  2
Bronchospasm  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Pneumonitis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Infection (chest) with normal ANC  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Pleural effusion  1  2/193 (1.04%)  2 0/193 (0.00%)  0
Pleural pain  1  0/193 (0.00%)  0 1/193 (0.52%)  1
Pneumothorax  1  1/193 (0.52%)  1 0/193 (0.00%)  0
Haemoptysis  1  0/193 (0.00%)  0 1/193 (0.52%)  1
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A: NGR-hTNF + BIC B: Placebo+BIC
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   190/193 (98.45%)      185/193 (95.85%)    
Blood and lymphatic system disorders     
Neutropenia  1  57/193 (29.53%)  162 60/193 (31.09%)  119
Anaemia  1  34/193 (17.62%)  58 42/193 (21.76%)  79
Thrombocytopenia  1  26/193 (13.47%)  56 23/193 (11.92%)  47
Leukopenia  1  24/193 (12.44%)  85 20/193 (10.36%)  24
Gastrointestinal disorders     
Nausea  1  61/193 (31.61%)  122 62/193 (32.12%)  130
Constipation  1  42/193 (21.76%)  65 45/193 (23.32%)  65
Vomiting  1  33/193 (17.10%)  61 38/193 (19.69%)  81
Diarrhoea  1  20/193 (10.36%)  39 36/193 (18.65%)  58
Dyspepsia  1  10/193 (5.18%)  12 11/193 (5.70%)  13
Abdominal disconfort  1  1/193 (0.52%)  1 11/193 (5.70%)  12
General disorders     
Chills  1  104/193 (53.89%)  462 23/193 (11.92%)  29
Fatigue  1  93/193 (48.19%)  166 94/193 (48.70%)  180
Pain  1  91/193 (47.15%)  179 89/193 (46.11%)  184
Pyrexia  1  48/193 (24.87%)  103 39/193 (20.21%)  67
Oedema  1  26/193 (13.47%)  31 25/193 (12.95%)  29
Mucosal inflammation  1  20/193 (10.36%)  29 17/193 (8.81%)  23
Infections and infestations     
Respiratory tract infection  1  13/193 (6.74%)  15 10/193 (5.18%)  13
Investigations     
Transaminases Increased  1  14/193 (7.25%)  37 7/193 (3.63%)  20
Metabolism and nutrition disorders     
Decreased appetite  1  46/193 (23.83%)  68 51/193 (26.42%)  76
Hypocalcaemia  1  12/193 (6.22%)  21 5/193 (2.59%)  6
Nervous system disorders     
Dizziness  1  11/193 (5.70%)  12 12/193 (6.22%)  14
Dysgeusia  1  10/193 (5.18%)  10 6/193 (3.11%)  7
Headache  1  15/193 (7.77%)  16 13/193 (6.74%)  15
Pheripheral neuropathy  1  12/193 (6.22%)  20 12/193 (6.22%)  15
Psychiatric disorders     
Insomnia  1  11/193 (5.70%)  12 12/193 (6.22%)  12
Respiratory, thoracic and mediastinal disorders     
Dysponoea  1  63/193 (32.64%)  94 56/193 (29.02%)  80
Cough  1  39/193 (20.21%)  59 47/193 (24.35%)  71
Skin and subcutaneous tissue disorders     
Alopecia  1  12/193 (6.22%)  12 4/193 (2.07%)  4
Pruritus  1  11/193 (5.70%)  15 8/193 (4.15%)  8
Vascular disorders     
Hypertension  1  12/193 (6.22%)  16 12/193 (6.22%)  15
Hypotension  1  10/193 (5.18%)  12 7/193 (3.63%)  9
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Operations
Organization: Molmed S.p.A
Phone: 003902212771
EMail: clinical.operations@molmed.com
Layout table for additonal information
Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT01098266     History of Changes
Other Study ID Numbers: NGR015
2009-016879-29 ( EudraCT Number )
First Submitted: March 17, 2010
First Posted: April 2, 2010
Results First Submitted: June 5, 2019
Results First Posted: September 17, 2019
Last Update Posted: September 17, 2019