Cisplatin + Etoposide +/- Concurrent ZD6474 in Previously Untreated Extensive Stage Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00613626
First received: January 31, 2008
Last updated: May 21, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Small Cell Lung Cancer
Drug: Cisplatin
Drug: Etoposide
Drug: Placebo
Drug: ZD6474
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • The primary objective will be to evaluate whether the addition of ZD6474 to EP improves time to disease progression over EP alone. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the safety and tolerability of this treatment combination [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Measure the response rate (CR + PR) in each arm [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Measure disease control rate (CR + PR+ SD) in each arm [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Measure overall survival for each arm [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Assess VEGF Polymorphisms and correlate subject response [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: January 2008
Estimated Study Completion Date: January 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: A
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.
Drug: Cisplatin
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Drug: Etoposide
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
Drug: Placebo
Matched placebo oral daily
Active Comparator: B
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.
Drug: Cisplatin
Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles
Drug: Etoposide
Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles
Drug: ZD6474
ZD6474 100mg oral daily to be continued for the duration of the study.

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00613626

Locations
United States, Delaware
Helen F. Graham Cancer Center
Newark, Delaware, United States, 19713
United States, Illinois
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States, 60611
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States, 47714
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
IN Onc/Hem Associates
Indianapolis, Indiana, United States, 46202
St. Vincent Hospital & Health Centers
Indianapolis, Indiana, United States, 46206
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Horizon Oncology Researcg
Lafayette, Indiana, United States, 47905
IU Health Arnett Cancer Center
Lafayette, Indiana, United States, 47904
IU Health at Ball Memorial Hospital
Muncie, Indiana, United States, 47303
Monroe Medical Associates
Munster, Indiana, United States, 46321
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Nebraska
Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Hematology Oncology Associates S.J., P.A.
Mt. Holly, New Jersey, United States, 08060
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
Pennsylvania Oncology-Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Sponsors and Collaborators
Hoosier Cancer Research Network
AstraZeneca
Investigators
Study Chair: Nasser Hanna, M.D. Hoosier Oncology Group, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00613626     History of Changes
Other Study ID Numbers: LUN06-113
Study First Received: January 31, 2008
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Hoosier Cancer Research Network:
Extensive Stage
Untreated

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Cisplatin
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 23, 2014