Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer
7 février 2020 mis à jour par: Hoosier Cancer Research Network
A Randomized Double Blind Phase II Trial of Cisplatin Plus Etoposide With/Without Concurrent ZD6474 in Patients With Previously Untreated Extensive Stage Small Cell Lung Cancer: Hoosier Oncology Group LUN06-113
At this point in the treatment of extensive stage SCLC, we have reached a plateau in survival with conventional chemotherapy and newer regimens are greatly needed.
It has been noted that patients with increased VEGF levels have a poorer prognosis.
Anti-angiogenic agents hold significant promise in the treatment of patients with extensive stage SCLC.
ZD6474, a new inhibitor of the VEGFR-2, has shown favorable action in NSCLC.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
OUTLINE: This is a multi-center study.
Arm A:
Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + Placebo oral daily given continuously for the duration of the study
Arm B:
Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + ZD6474 100mg oral daily given continuously for the duration of the study
For both arms, PE and toxicity evaluation prior to each cycle and disease assessment by imaging every 2 cycles. Patients with non-PD and acceptable toxicity will continue protocol therapy; patients with progressive disease or excessive toxicity will be taken off treatment. Cycles will be repeated every 21 days up to a total of 4 cycles.
ECOG Performance Status of 0 or 1
Life Expectancy: Not specified
Hematopoietic:
- Platelets > 100K/mm3
- Absolute neutrophil count (ANC) > 1.5K/mm3
Hepatic:
- Bilirubin < 1.5 x ULN
- Aspartate aminotransferase (AST) < 2.5 x ULN or < 5 x ULN if judged by the investigator to be related to liver metastases
- Alkaline phosphatase < 2.5 x ULN or < 5 x ULN if judged by the investigator to be related to liver metastases
Renal:
- Serum creatinine < 1.5 x ULN or Calculated creatinine clearance of > 45 cc/min using the Cockcroft-Gault formula
Cardiovascular:
- No clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >2 (see SPM) within 3 months prior to registration for protocol therapy
- No presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
- No history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is permitted.
Type d'étude
Interventionnel
Inscription (Réel)
74
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Delaware
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Newark, Delaware, États-Unis, 19713
- Helen F. Graham Cancer Center
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Illinois
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Chicago, Illinois, États-Unis, 60611
- Northwestern University Feinberg School of Medicine
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Galesburg, Illinois, États-Unis, 61401
- Medical & Surgical Specialists, LLC
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Indiana
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Bloomington, Indiana, États-Unis, 47403
- Cancer Care Center of Southern Indiana
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Evansville, Indiana, États-Unis, 47714
- Oncology Hematology Associates of SW Indiana
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Fort Wayne, Indiana, États-Unis, 46815
- Fort Wayne Oncology & Hematology, Inc
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Indianapolis, Indiana, États-Unis, 46202
- Indiana University Simon Cancer Center
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Indianapolis, Indiana, États-Unis, 46202
- IN Onc/Hem Associates
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Indianapolis, Indiana, États-Unis, 46206
- St. Vincent Hospital & Health Centers
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Lafayette, Indiana, États-Unis, 47904
- IU Health Arnett Cancer Center
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Lafayette, Indiana, États-Unis, 47905
- Horizon Oncology Researcg
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Muncie, Indiana, États-Unis, 47303
- IU Health at Ball Memorial Hospital
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Munster, Indiana, États-Unis, 46321
- Monroe Medical Associates
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South Bend, Indiana, États-Unis, 46601
- Northern Indiana Cancer Research Consortium
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Terre Haute, Indiana, États-Unis, 47802
- Providence Medical Group
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Nebraska
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Omaha, Nebraska, États-Unis, 68114
- Methodist Cancer Center
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New Jersey
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Mount Holly, New Jersey, États-Unis, 08060
- Hematology Oncology Associates S.J., P.A.
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Oregon
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Portland, Oregon, États-Unis, 97213
- Providence Portland Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19106
- Pennsylvania Oncology-Hematology Associates
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Histological or cytological proof of chemotherapy-naïve, extensive, small cell lung cancer.
- Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy.
- Written informed consent and HIPAA authorization for release of personal health information.
- Age 18 years or older at the time of consent.
- Potassium ≥4.0 mmol/L and <5.5mmol/L (supplementation is allowed).
- Calcium within normal range (supplementation is allowed).
- Magnesium within normal range (supplementation is allowed).
Exclusion Criteria:
- No prior EGFR inhibitor or antiangiogenic agent allowed.
- No prior hormonal therapy.
- No symptomatic brain metastasis.
- No clinically significant infections as judged by the treating investigator.
- No evidence of severe or uncontrolled other systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
- No previous history of QTc prolongation as a result of medication that required discontinuation of that medication.
- No congenital long QT syndrome or known 1st degree relative with unexplained sudden death under 40 years of age.
- No presence of left bundle branch block (LBBB.)
- No QTc with Bazett's correction that is unmeasurable, or ≥480 msec on screening ECG obtained within 7 days prior to registration for protocol therapy. If a subject has QTc ≥480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study.
- No concomitant (within 14 days prior to registration for and during protocol therapy) medication associated with Torsades de Pointes or cause QTc prolongation, is allowed. Medications that prolong QT, but are not strictly associated with Torsades, are allowed if medically necessary and will require increased ECG and electrolyte monitoring.
- No uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg).
- No currently active diarrhea that may affect the ability to absorb ZD6474.
- No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason < grade 7 prostate cancers, or other cancer for which the subject has been disease-free for at least 5 years.
- Major surgery must be completed greater than 28 days prior to registration for protocol therapy and healed surgical incision is required.
- No concomitant (within 14 days prior to registration for and during protocol therapy) medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function.
- Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
- Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
- Females must not be breastfeeding.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur placebo: Arm A: ZD6474 Matched Placebo
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 matched placebo oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
|
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
Matched placebo oral daily
|
|
Comparateur actif: Arm B: ZD6474
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
|
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
ZD6474 100mg oral daily to be continued for the duration of the study.
|
|
Expérimental: Safety Lead-In
Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study.
Prophylactic antiemetics will be given at the discretion of the treating investigator.
The safety lead-in will be conducted to determine the safety of the combination of ZD6474 and cisplation + etopiside.
If this combination is found to be unsafe, no patients will be randomized in the Phase II portion of the trial.
If the combination is deemed safe according to the protocol, participants from the safety lead-in cohort will not be included in the efficacy analysis.
|
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
ZD6474 100mg oral daily to be continued for the duration of the study.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Time to Disease Progression - Median Time to Progression and Log-Rank Test
Délai: 24 months
|
Kaplan-Meier analysis comparing arm A to arm B. Median time to progression and log-rank test.
Safety lead-in participants are not included in this analysis per protocol.
|
24 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities
Délai: 6 weeks (2 Cycles)
|
Percentage of participants who experienced grade 3/4 hematologic and non-hematologic toxicities.
Participants from Arm A were compared to subjects from Arm B + Safety Lead-In.
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6 weeks (2 Cycles)
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Measure the Response Rate (CR + PR) in Each Arm
Délai: 24 months
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Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000).
Complete Response (CR) is defined as: Disappearance of all target lesions.
Partial Response (PR) is defined as: >=30% decrease in the sum of the longest diameter of target lesions.
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24 months
|
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Measure Disease Control Rate (CR + PR+ SD) in Each Arm
Délai: 24 months
|
Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000).
Complete Response (CR) is defined as: Disappearance of all target lesions.
Partial Response (PR) is defined as: >=30% decrease in the sum of the longest diameter of target lesions.
Stable Disease (SD) is defined as: neither a partial response or progressive disease ( >=20% increase in the sum of the longest diameter of the target lesions).
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24 months
|
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Measure Overall Survival for Each Arm
Délai: 24 months
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24 months
|
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Assess VEGF Polymorphisms and Correlate Subject Response
Délai: 24 months
|
24 months
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Nasser Hanna, M.D., Hoosier Oncology Group, Inc.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 janvier 2008
Achèvement primaire (Réel)
1 août 2015
Achèvement de l'étude (Réel)
1 août 2015
Dates d'inscription aux études
Première soumission
31 janvier 2008
Première soumission répondant aux critères de contrôle qualité
31 janvier 2008
Première publication (Estimation)
13 février 2008
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
11 février 2020
Dernière mise à jour soumise répondant aux critères de contrôle qualité
7 février 2020
Dernière vérification
1 février 2020
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Tumeurs
- Maladies pulmonaires
- Tumeurs par site
- Tumeurs des voies respiratoires
- Tumeurs thoraciques
- Carcinome bronchique
- Tumeurs bronchiques
- Tumeurs pulmonaires
- Carcinome pulmonaire à petites cellules
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Étoposide
Autres numéros d'identification d'étude
- LUN06-113
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .