Trial Outcomes & Findings for Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Metastatic Small Cell Lung Carcinoma (NCT NCT00483509)

Last Updated: 2019-10-04

Results Overview

Defined as the time from the date of randomization until disease progression, or death due to any cause or the last patient was known to be alive. Progression is defined using 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 the appearance of one or more new lesions was also considered progression

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 150 weeks

Results posted on

2019-10-04

Participant Flow

Study period: February 14th, 2007 (first enrolment), April 23rd, 2010(last enrolment); May 17th, 2011(LPLV) 5 clinical sites in Italy

Planned sample size n.: 27 patients; Patient screened n.:28; Patient screening failure n.: 0

Participant milestones

Participant milestones
Measure	A: NGR-hTNF + Doxorubicin NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Overall Study STARTED	28
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Metastatic Small Cell Lung Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A: NGR-hTNF + Doxorubicin n=28 Participants NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=99 Participants
Age, Categorical >=65 years	12 Participants n=99 Participants
Age, Continuous	62.5 years n=99 Participants
Sex: Female, Male Female	9 Participants n=99 Participants
Sex: Female, Male Male	19 Participants n=99 Participants
Region of Enrollment Italy	28 participants n=99 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 150 weeks

Outcome measures

Outcome measures
Measure	A: NGR-hTNF + Doxorubicin n=28 Participants NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Antitumour Activity Defined as Progression Free Survival (PFS)	3.2 months Interval 1.8 to 4.7

SECONDARY outcome

Timeframe: Assessed every 6-12 weeks, up to 150 weeks

evaluated according to Response evaluation criteria in solid tumors (RECIST V1.0) for target lesions and assessed by MRI: * Complete Response (CR):Disappearance of all target lesions * Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the base line sum LD * Progressive Disease (PD): At least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	A: NGR-hTNF + Doxorubicin n=28 Participants NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Tumor Growth Control Rate (TGCR) Complete Response (CR)	0 Participants
Tumor Growth Control Rate (TGCR) Partial Response(PR)	7 Participants
Tumor Growth Control Rate (TGCR) Stable disease	8 Participants
Tumor Growth Control Rate (TGCR) Progressive disease (PD)	10 Participants
Tumor Growth Control Rate (TGCR) Not assessable	3 Participants

SECONDARY outcome

Timeframe: Through study completion, an average of 3 years

Overall Survival was defined as the time from the baseline CT scan to death due to any cause, or the last date the patient was known to be alive.

Outcome measures

Outcome measures
Measure	A: NGR-hTNF + Doxorubicin n=28 Participants NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Overall Survival (OS)	5.6 months Interval 5.3 to 5.9

SECONDARY outcome

Timeframe: during the study

Population: Though a DCE-MRI evaluation was planned by protocol for a selected number of patients, no DCE-MRI assessments were performed.

To document possible modifications on vessels permeability by imaging techniques

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through study completion, an average of 3 years

Evaluation according to NCI common terminology criteria for adverse events (version 3.0)

Outcome measures

Outcome measures
Measure	A: NGR-hTNF + Doxorubicin n=28 Participants NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Number of Adverse Events, Reported by Severity and Relation to Treatment NGR-hTNF Related Adverse Event	27 Event
Number of Adverse Events, Reported by Severity and Relation to Treatment Adverse Event	349 Event
Number of Adverse Events, Reported by Severity and Relation to Treatment Serious Adverse Event	12 Event
Number of Adverse Events, Reported by Severity and Relation to Treatment Doxorubicin AE Related Adverse Event	206 Event
Number of Adverse Events, Reported by Severity and Relation to Treatment NGR-hTNF + Doxorubicin Related Adverse Event	4 Event

Adverse Events

A: NGR-hTNF + Doxorubicin

Serious events: 7 serious events

Other events: 28 other events

Deaths: 28 deaths

Serious adverse events

Serious adverse events
Measure	A: NGR-hTNF + Doxorubicin n=28 participants at risk NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Febrile neutropenia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Neutopenia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Anaemia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Nervous system disorders Seizure	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Infectious Fever	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Mucosal Inflammation	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Enteritis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Stomatitis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Muscular weakness	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Wound infection	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Pneumonia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years

Other adverse events

Other adverse events
Measure	A: NGR-hTNF + Doxorubicin n=28 participants at risk NGR-hTNF plus doxorubicin NGR-hTNF: iv q3W 0.8 mcg/sqm NGR-hTNF Doxorubicin: iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Cardiac disorders Aortic vlave incompetence	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Aortic valve sclerosis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Atrial fibrillation	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Atrial Hypertofhy	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Bundle branch block bilateral	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Bundle branch block right	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders Mitral valve incompetence	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Cardiac disorders Pericardial effusion	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Cardiac disorders synus tachycardia	10.7% 3/28 • Number of events 3 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Anaemia	57.1% 16/28 • Number of events 17 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Febrile neutopenia	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Leukopenia	64.3% 18/28 • Number of events 42 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Lymphopenia	42.9% 12/28 • Number of events 15 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Neutropenia	60.7% 17/28 • Number of events 38 • Through study completion, an average of 3 years
Blood and lymphatic system disorders Thrombocytopenia	35.7% 10/28 • Number of events 20 • Through study completion, an average of 3 years
Eye disorders Conjunctivitis	10.7% 3/28 • Number of events 4 • Through study completion, an average of 3 years
Eye disorders Eyelid ptosis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Constipation	17.9% 5/28 • Number of events 5 • Through study completion, an average of 3 years
Gastrointestinal disorders Diarrohea	14.3% 4/28 • Number of events 7 • Through study completion, an average of 3 years
Gastrointestinal disorders Enteritis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Gastritis	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Gastrointestinal disorders Glossodynia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Nausea	42.9% 12/28 • Number of events 14 • Through study completion, an average of 3 years
Gastrointestinal disorders Regurgitation	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Gastrointestinal disorders Vomiting	17.9% 5/28 • Number of events 8 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Alopecia	10.7% 3/28 • Number of events 3 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Dri Skin	10.7% 3/28 • Number of events 3 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Nail disorder	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Pruritus	10.7% 3/28 • Number of events 5 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Skin exfoliation	7.1% 2/28 • Number of events 3 • Through study completion, an average of 3 years
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Back pain	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Bone pain	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Monarthritis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Neck pain	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Musculoskeletal and connective tissue disorders Osteoarthritis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Anorexia	35.7% 10/28 • Number of events 11 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Hyperurricaemia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Hypocalcaemia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Hypokalemia	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Hyponatraemia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Metabolism and nutrition disorders Metabolism acidosis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Injury, poisoning and procedural complications Allergic transfusion reaction	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Injury, poisoning and procedural complications Injury	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Vascular disorders Flushing	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Vascular disorders Hypertension	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Vascular disorders Hypotension	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Vascular disorders Phlebitis	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
General disorders Asthenia	17.9% 5/28 • Number of events 6 • Through study completion, an average of 3 years
General disorders Chills	53.6% 15/28 • Number of events 20 • Through study completion, an average of 3 years
General disorders Extravasation	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Fatigue	46.4% 13/28 • Number of events 14 • Through study completion, an average of 3 years
General disorders Feeling cold	10.7% 3/28 • Number of events 3 • Through study completion, an average of 3 years
General disorders Injection site pain	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Injection site reaction	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Mucosal Inflammation	21.4% 6/28 • Number of events 9 • Through study completion, an average of 3 years
General disorders Oedema	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
General disorders Pyrexia	28.6% 8/28 • Number of events 8 • Through study completion, an average of 3 years
General disorders Wound Infection	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Bronchitis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Oral candidiasis	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Pneumonia	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Infections and infestations Respiratori tract infection	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Infections and infestations Urinary tract infection	10.7% 3/28 • Number of events 3 • Through study completion, an average of 3 years
Psychiatric disorders Confusional state	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Psychiatric disorders Deprerssion	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Psychiatric disorders Insomnia	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Reproductive system and breast disorders Pelvic pain	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Investigations Aspartate aminotransferase increased	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Investigations Blood alkaline phosphatase increased	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Investigations Blood uric acid increased	3.6% 1/28 • Number of events 2 • Through study completion, an average of 3 years
Investigations Blood biliribin increased	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Investigations Electrocardiogram abnormal	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Investigations Gamma-glutamyltransferase increased	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Cough	14.3% 4/28 • Number of events 4 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.9% 5/28 • Number of events 6 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Hiccups	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Hipoxia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Increased bronchial secretion	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Respiratory, thoracic and mediastinal disorders Rhinorrea	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Nervous system disorders Convulsion	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Nervous system disorders Dizziness	7.1% 2/28 • Number of events 2 • Through study completion, an average of 3 years
Nervous system disorders Headache	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Nervous system disorders Hypotonia	3.6% 1/28 • Number of events 1 • Through study completion, an average of 3 years
Nervous system disorders Paraesthesia	7.1% 2/28 • Number of events 3 • Through study completion, an average of 3 years

Additional Information

Clinical Operations

Molmed S.p.A

Phone: 003902212771

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place