Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer
7 februari 2020 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
74
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Delaware
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Newark, Delaware, Förenta staterna, 19713
- Helen F. Graham Cancer Center
-
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Illinois
-
Chicago, Illinois, Förenta staterna, 60611
- Northwestern University Feinberg School of Medicine
-
Galesburg, Illinois, Förenta staterna, 61401
- Medical & Surgical Specialists, LLC
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Indiana
-
Bloomington, Indiana, Förenta staterna, 47403
- Cancer Care Center of Southern Indiana
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Evansville, Indiana, Förenta staterna, 47714
- Oncology Hematology Associates of SW Indiana
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Fort Wayne, Indiana, Förenta staterna, 46815
- Fort Wayne Oncology & Hematology, Inc
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Indianapolis, Indiana, Förenta staterna, 46202
- Indiana University Simon Cancer Center
-
Indianapolis, Indiana, Förenta staterna, 46202
- IN Onc/Hem Associates
-
Indianapolis, Indiana, Förenta staterna, 46206
- St. Vincent Hospital & Health Centers
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Lafayette, Indiana, Förenta staterna, 47904
- IU Health Arnett Cancer Center
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Lafayette, Indiana, Förenta staterna, 47905
- Horizon Oncology Researcg
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Muncie, Indiana, Förenta staterna, 47303
- IU Health at Ball Memorial Hospital
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Munster, Indiana, Förenta staterna, 46321
- Monroe Medical Associates
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South Bend, Indiana, Förenta staterna, 46601
- Northern Indiana Cancer Research Consortium
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Terre Haute, Indiana, Förenta staterna, 47802
- Providence Medical Group
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Nebraska
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Omaha, Nebraska, Förenta staterna, 68114
- Methodist Cancer Center
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New Jersey
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Mount Holly, New Jersey, Förenta staterna, 08060
- Hematology Oncology Associates S.J., P.A.
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Oregon
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Portland, Oregon, Förenta staterna, 97213
- Providence Portland Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Förenta staterna, 19106
- Pennsylvania Oncology-Hematology Associates
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-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Placebo-jämförare: 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
|
|
Aktiv komparator: 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.
|
|
Experimentell: 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.
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Time to Disease Progression - Median Time to Progression and Log-Rank Test
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities
Tidsram: 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.
|
6 weeks (2 Cycles)
|
|
Measure the Response Rate (CR + PR) in Each Arm
Tidsram: 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.
|
24 months
|
|
Measure Disease Control Rate (CR + PR+ SD) in Each Arm
Tidsram: 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).
|
24 months
|
|
Measure Overall Survival for Each Arm
Tidsram: 24 months
|
24 months
|
|
|
Assess VEGF Polymorphisms and Correlate Subject Response
Tidsram: 24 months
|
24 months
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Utredare
- Studiestol: Nasser Hanna, M.D., Hoosier Oncology Group, Inc.
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 januari 2008
Primärt slutförande (Faktisk)
1 augusti 2015
Avslutad studie (Faktisk)
1 augusti 2015
Studieregistreringsdatum
Först inskickad
31 januari 2008
Först inskickad som uppfyllde QC-kriterierna
31 januari 2008
Första postat (Uppskatta)
13 februari 2008
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
11 februari 2020
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
7 februari 2020
Senast verifierad
1 februari 2020
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Luftvägssjukdomar
- Neoplasmer
- Lungsjukdomar
- Neoplasmer efter plats
- Neoplasmer i andningsvägarna
- Thoracic neoplasmer
- Karcinom, bronkogent
- Bronkiella neoplasmer
- Lungneoplasmer
- Småcelligt lungkarcinom
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antineoplastiska medel
- Antineoplastiska medel, fytogena
- Topoisomeras II-hämmare
- Topoisomerasinhibitorer
- Etoposid
Andra studie-ID-nummer
- LUN06-113
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