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

NCT ID: NCT00613626

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2015-08-31

Brief Summary

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.

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.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Cisplatin

Intervention Type: DRUG

Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide

Intervention Type: DRUG

Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

Placebo

Intervention Type: DRUG

Matched placebo oral daily

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.

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide

Intervention Type: DRUG

Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474

Intervention Type: DRUG

ZD6474 100mg oral daily to be continued for the duration of the study.

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.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Etoposide

Intervention Type: DRUG

Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

ZD6474

Intervention Type: DRUG

ZD6474 100mg oral daily to be continued for the duration of the study.

Interventions

Cisplatin

Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles

Intervention Type: DRUG

Etoposide

Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles

Intervention Type: DRUG

Placebo

Matched placebo oral daily

Intervention Type: DRUG

ZD6474

ZD6474 100mg oral daily to be continued for the duration of the study.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nasser Hanna, M.D.

Role: STUDY_CHAIR

Hoosier Oncology Group, Inc.

Locations

Helen F. Graham Cancer Center

Newark, Delaware, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Cancer Care Center of Southern Indiana

Bloomington, Indiana, United States

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, United States

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, United States

IN Onc/Hem Associates

Indianapolis, Indiana, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

St. Vincent Hospital & Health Centers

Indianapolis, Indiana, United States

IU Health Arnett Cancer Center

Lafayette, Indiana, United States

Horizon Oncology Researcg

Lafayette, Indiana, United States

IU Health at Ball Memorial Hospital

Muncie, Indiana, United States

Monroe Medical Associates

Munster, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Providence Medical Group

Terre Haute, Indiana, United States

Methodist Cancer Center

Omaha, Nebraska, United States

Hematology Oncology Associates S.J., P.A.

Mount Holly, New Jersey, United States

Providence Portland Medical Center

Portland, Oregon, United States

Pennsylvania Oncology-Hematology Associates

Philadelphia, Pennsylvania, United States

Countries

United States

References

Rachel E. Sanborn, Jyoti D. Patel, Gregory A. Masters, Nagesh Jayaram, Anthony W. Stephens, Michael J. Guarino, Jamal Ghazi Misleh, Corinne E. Williams, Jingwei Wu, Nasser H. Hanna. A randomized double-blind phase II trial of platinum (P) plus etoposide (E) with or without concurrent ZD6474 (Z) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC): Hoosier Oncology Group LUN06-113. J Clin Oncol 32:5s, 2014 (suppl; abstr 7506)

Reference Type: RESULT

Related Links

http://www.hoosieroncologygroup.org

Hoosier Oncology Group Home Page

Other Identifiers

LUN06-113

Identifier Type: -

Identifier Source: org_study_id