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A Study of Aflibercept Administered in Combination With Pemetrexed and Cisplatin in Participants With Advanced Carcinoma
Phase 1, PHASE2 trial testing Aflibercept in Advanced Carcinoma in 60 participants. Terminated before completion.
| Lead sponsor | Regeneron Pharmaceuticals |
|---|---|
| Phase | Phase 1, PHASE2 |
| Status | Terminated |
| Study type | INTERVENTIONAL |
| Allocation | non randomized |
| Design | single group |
| Masking | none |
| Primary purpose | treatment |
| Enrollment | 60 |
| Start date | 30 November 2008 |
| Primary completion | 30 June 2011 |
| Estimated completion | 30 June 2011 |
| Sites | 15 locations across Canada, United States |
Regeneron Pharmaceuticals — full company profile →
18 and older, any sex, with Advanced Carcinoma or Non-small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Recommended Dose was defined as the highest combination dose at which fewer than 33 percent (%) of participants experienced dose limiting toxicity during the first cycle of therapy.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: All Participants | 6 |
Objective response rate was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by modified Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the Baseline sum LD as reference.
| Group | Value | 95% CI |
|---|---|---|
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 23.8 |
PFS was defined as the time in days from the date of first study drug administration to the date of first documentation of tumor progression or death from any cause, whichever occurs first, as assessed by the modified RECIST. Median time of PFS was estimated using Kaplan-Meier method.
| Group | Value | 95% CI |
|---|---|---|
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 149 | 130 – 212 |
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (for example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. Any TEAE includ
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 4 | |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 7 | |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 7 | |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 42 |
The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 201 | ± 96.5 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 330 | ± 251 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 442 | ± 152 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 402 | ± 100 |
The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 151 | ± 30.0 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 151 | ± 32.5 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 162 | ± 12.6 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 148 | ± 24.3 |
Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 53.6 | ± 7.14 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 68.6 | ± 18.7 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 148 | ± 108 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 104 | ± 26.2 |
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 124 | ± 12.6 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 112 | ± 34.7 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 113 | ± 24.6 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 76.8 | ± 40.5 |
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 0.011 | ± 0.004 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 0.016 | ± 0.007 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 0.016 | ± 0.009 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 0.016 | ± 0.004 |
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 3.40 | ± 0.59 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 3.47 | ± 0.84 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 3.10 | ± 0.22 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 3.49 | ± 0.76 |
Terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 3.16 | ± 0.570 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 5.53 | ± 5.43 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 3.72 | ± 1.04 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 4.62 | ± 1.46 |
Terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 1.47 | ± 0.39 |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 1.63 | ± 0.22 |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 1.73 | ± 0.37 |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 1.48 | ± 0.34 |
Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of ADA.
| Group | Value | 95% CI |
|---|---|---|
| Phase 1: Aflibercept 2 mg/kg and Pemetrexed and Cisplatin | 0 | |
| Phase 1: Aflibercept 4 mg/kg and Pemetrexed and Cisplatin | 0 | |
| Phase 1: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 1 | |
| Phase 2: Aflibercept 6 mg/kg and Pemetrexed and Cisplatin | 2 |
Time frame: All Adverse Events (AEs) were collected from signature of the informed consent form up to 751 Days for Phase 1 and 972 Days for Phase 2 regardless of seriousness or relationship to investigational product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Phase 1: Aflibercept 2 mg/… | Phase 1: Aflibercept 4 mg/… | Phase 1: Aflibercept 6 mg/… | Phase 2: Aflibercept 6 mg/… |
|---|---|---|---|---|---|
| DISEASE PROGRESSION | General disorders | — | — | — | — |
| HYPERTENSION | Vascular disorders | — | — | — | — |
| REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME | Nervous system disorders | — | — | — | — |
| RENAL FAILURE ACUTE | Renal and urinary disorders | — | — | — | — |
| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| PNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| PNEUMONIA | Infections and infestations | — | — | — | — |
| HEADACHE | Nervous system disorders | — | — | — | — |
| CHOLANGITIS | Hepatobiliary disorders | — | — | — | — |
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| HAEMOPTYSIS | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| HYDROPNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| FATIGUE | General disorders | — | — | — | — |
| CHEST PAIN | General disorders | — | — | — | — |
| METASTATIC PAIN | General disorders | — | — | — | — |
| HYPOTENSION | Vascular disorders | — | — | — | — |
| GINGIVAL INFECTION | Infections and infestations | — | — | — | — |
| BRONCHITIS | Infections and infestations | — | — | — | — |
| PNEUMOCOCCAL SEPSIS | Infections and infestations | — | — | — | — |
| URINARY TRACT INFECTION | Infections and infestations | — | — | — | — |
| ATRIAL FIBRILLATION | Cardiac disorders | — | — | — | — |
| MUSCULOSKELETAL CHEST PAIN | Musculoskeletal and connective tissue disorders | — | — | — | — |
| METASTATIC PAIN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — | — | — |
| Reaction | System | Phase 1: Aflibercept 2 mg/… | Phase 1: Aflibercept 4 mg/… | Phase 1: Aflibercept 6 mg/… | Phase 2: Aflibercept 6 mg/… |
|---|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | — | — | — | — |
| FATIGUE | General disorders | — | — | — | — |
| CONSTIPATION | Gastrointestinal disorders | — | — | — | — |
| HYPERTENSION | Vascular disorders | — | — | — | — |
| DIARRHOEA | Gastrointestinal disorders | — | — | — | — |
| STOMATITIS | Gastrointestinal disorders | — | — | — | — |
| DYSGEUSIA | Nervous system disorders | — | — | — | — |
| DYSPHONIA | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| PROTEINURIA | Renal and urinary disorders | — | — | — | — |
| HEADACHE | Nervous system disorders | — | — | — | — |
| ANOREXIA | Metabolism and nutrition disorders | — | — | — | — |
| DYSPEPSIA | Gastrointestinal disorders | — | — | — | — |
| DEHYDRATION | Metabolism and nutrition disorders | — | — | — | — |
| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| VOMITING | Gastrointestinal disorders | — | — | — | — |
| WEIGHT LOSS POOR | Metabolism and nutrition disorders | — | — | — | — |
| BLOOD CREATININE INCREASED | Investigations | — | — | — | — |
| HYPONATRAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| COUGH | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| NEUTROPENIA | Blood and lymphatic system disorders | — | — | — | — |
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | — | — | — | — |
| DIZZINESS | Nervous system disorders | — | — | — | — |
| INSOMNIA | Nervous system disorders | — | — | — | — |
| HYPOMAGNESAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| DRY MOUTH | Gastrointestinal disorders | — | — | — | — |
| OEDEMA PERIPHERAL | General disorders | — | — | — | — |
| HYPOKALAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| HYPERKALAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| HYPOCALCAEMIA | Metabolism and nutrition disorders | — | — | — | — |
| HICCUPS | Respiratory, thoracic and mediastinal disorders | — | — | — | — |
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | — | — | — | — |
| MYALGIA | Musculoskeletal and connective tissue disorders | — | — | — | — |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | — | — | — | — |
| ANAEMIA | Blood and lymphatic system disorders | — | — | — | — |
| FEELING ABNORMAL | General disorders | — | — | — | — |
| ASTHENIA | General disorders | — | — | — | — |
| NEUROPATHY PERIPHERAL | Nervous system disorders | — | — | — | — |
Most-reported serious reactions: DISEASE PROGRESSION, HYPERTENSION, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME, RENAL FAILURE ACUTE, PULMONARY EMBOLISM, DYSPNOEA, PNEUMOTHORAX, PNEUMONIA.
Data from ClinicalTrials.gov NCT00794417 adverse events section.
The purpose of the study was to determine whether the combination of aflibercept, pemetrexed and cisplatin is safe and effective in treating non-small cell lung cancer (NSCLC).
3 peer-reviewed publications reference this trial (live from Europe PMC):
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