Small Cell Lung Cancer
Conditions
Keywords
NGR-hTNF, SCLC
Brief summary
The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic small cell lung carcinoma (SCLC) patients previously treated with at least one therapeutic regimen
Detailed description
This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic SCLC, previously treated with at least one therapeutic regimen, that will be conducted using Simon's two-stage design method.
Interventions
DRUGNGR-hTNF
iv q3W 0.8 mcg/sqm NGR-hTNF
DRUGDoxorubicin
iv q3W 75 mg/sqm doxorubicin 60 minutes after NGR-hTNF infusion
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years affected by SCLC previously treated with at least one therapeutic regimen (including doxorubicin). However, in case of patient already pretreated with doxorubicin, a previous cumulative dose of doxorubicin \< 300 mg/m\^2 is recommended and the current treatment has to be stopped when a maximum cumulative dose of doxorubicin 550 mg/m\^2 is reached. * Cytology or histology confirmed SCLC at first diagnosis (patient with recurrent disease do not require a confirmatory biopsy to be eligible) * Measurable disease, defined as ≥ 1 unidimensional measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by CT scan according to RECIST criteria * ECOG Performance status 0 - 2 * Adequate baseline bone marrow, hepatic and renal function, defined as follows: * Neutrophils \> 1.5 x 10\^9/L and platelets \> 100 x 10\^9/L * Bilirubin \< 1.5 x ULN * AST and/or ALT \< 2.5 x ULN in absence of liver metastasis * AST and/or ALT \< 5 x ULN in presence of liver metastasis * Serum creatinine \< 1.5 x ULN * Normal cardiac function (LVEF ≥ 55%) and absence of uncontrolled hypertension * Patients may have had prior therapy providing the following conditions are met: \- Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out period of 28 days before start treatment \- Surgery: wash-out period of 14 days before start treatment * Patients must give written informed consent to participate in the study
Exclusion criteria
* Concurrent anticancer therapy * Patients may not receive any other investigational agents while on study * Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication * Uncontrolled hypertension * Prolonged QTc interval (congenital or acquired) * Patient with significant peripheral vascular disease * Previous signs of cardiotoxicity doxorubicin related * Clinical signs of CNS involvement * Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients * Known hypersensitivity/allergic reaction or contraindications to anthracyclines * Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Antitumour Activity Defined as Progression Free Survival (PFS) | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Growth Control Rate (TGCR) | 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. |
| Overall Survival (OS) | 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. |
| Experimental Imaging Study (DCE-MRI) | during the study | To document possible modifications on vessels permeability by imaging techniques |
| Number of Adverse Events, Reported by Severity and Relation to Treatment | Through study completion, an average of 3 years | Evaluation according to NCI common terminology criteria for adverse events (version 3.0) |
Countries
Italy
Participant flow
Recruitment details
Study period: February 14th, 2007 (first enrolment), April 23rd, 2010(last enrolment); May 17th, 2011(LPLV) 5 clinical sites in Italy
Pre-assignment details
Planned sample size n.: 27 patients; Patient screened n.:28; Patient screening failure n.: 0
Participants by arm
| Arm | Count |
|---|---|
| A: NGR-hTNF + Doxorubicin 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 | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | A: NGR-hTNF + Doxorubicin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 62.5 years |
| Region of Enrollment Italy | 28 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 28 / 28 |
| other Total, other adverse events | 28 / 28 |
| serious Total, serious adverse events | 7 / 28 |
Outcome results
Primary
Antitumour Activity Defined as Progression Free Survival (PFS)
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
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: NGR-hTNF + Doxorubicin | Antitumour Activity Defined as Progression Free Survival (PFS) | 3.2 months |
Secondary
Experimental Imaging Study (DCE-MRI)
To document possible modifications on vessels permeability by imaging techniques
Time frame: 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.
Secondary
Number of Adverse Events, Reported by Severity and Relation to Treatment
Evaluation according to NCI common terminology criteria for adverse events (version 3.0)
Time frame: Through study completion, an average of 3 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A: NGR-hTNF + Doxorubicin | Number of Adverse Events, Reported by Severity and Relation to Treatment | NGR-hTNF Related Adverse Event | 27 Event |
| A: NGR-hTNF + Doxorubicin | Number of Adverse Events, Reported by Severity and Relation to Treatment | Adverse Event | 349 Event |
| A: NGR-hTNF + Doxorubicin | Number of Adverse Events, Reported by Severity and Relation to Treatment | Serious Adverse Event | 12 Event |
| A: NGR-hTNF + Doxorubicin | Number of Adverse Events, Reported by Severity and Relation to Treatment | Doxorubicin AE Related Adverse Event | 206 Event |
| A: NGR-hTNF + Doxorubicin | Number of Adverse Events, Reported by Severity and Relation to Treatment | NGR-hTNF + Doxorubicin Related Adverse Event | 4 Event |
Secondary
Overall Survival (OS)
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.
Time frame: Through study completion, an average of 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: NGR-hTNF + Doxorubicin | Overall Survival (OS) | 5.6 months |
Secondary
Tumor Growth Control Rate (TGCR)
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.
Time frame: Assessed every 6-12 weeks, up to 150 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A: NGR-hTNF + Doxorubicin | Tumor Growth Control Rate (TGCR) | Complete Response (CR) | 0 Participants |
| A: NGR-hTNF + Doxorubicin | Tumor Growth Control Rate (TGCR) | Partial Response(PR) | 7 Participants |
| A: NGR-hTNF + Doxorubicin | Tumor Growth Control Rate (TGCR) | Stable disease | 8 Participants |
| A: NGR-hTNF + Doxorubicin | Tumor Growth Control Rate (TGCR) | Progressive disease (PD) | 10 Participants |
| A: NGR-hTNF + Doxorubicin | Tumor Growth Control Rate (TGCR) | Not assessable | 3 Participants |