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

NCT00613626 | Completed Phase 2 Results DMC

• 1 other identifier: LUN06-113
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 19

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.

Conditions

Small Cell Lung Cancer

Keywords

Extensive Stage; Untreated

Outcome Measures

Primary Outcomes (1)

• Time to Disease Progression - Median Time to Progression and Log-Rank Test

  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

Secondary Outcomes (5)

• Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities

  6 weeks (2 Cycles)

• Measure the Response Rate (CR + PR) in Each Arm

  24 months

• Measure Disease Control Rate (CR + PR+ SD) in Each Arm

  24 months

• Measure Overall Survival for Each Arm

  24 months

• Assess VEGF Polymorphisms and Correlate Subject Response

  24 months

Study Arms (3)

Arm A: ZD6474 Matched Placebo

PLACEBO COMPARATOR

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; Drug: Etoposide; Drug: Placebo

Arm B: ZD6474

ACTIVE COMPARATOR

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; Drug: Etoposide; Drug: ZD6474

Safety Lead-In

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Etoposide; Drug: ZD6474

Interventions

Cisplatin DRUG

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

Arm A: ZD6474 Matched Placebo; Arm B: ZD6474; Safety Lead-In

Etoposide DRUG

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

Arm A: ZD6474 Matched Placebo; Arm B: ZD6474; Safety Lead-In

Placebo DRUG

Matched placebo oral daily

Arm A: ZD6474 Matched Placebo

ZD6474 DRUG

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

Arm B: ZD6474; Safety Lead-In

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• AstraZeneca: collaborator

Study Sites (19)

Helen F. Graham Cancer Center

Newark, Delaware, 19713, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Medical & Surgical Specialists, LLC

Galesburg, Illinois, 61401, United States

Location

Cancer Care Center of Southern Indiana

Bloomington, Indiana, 47403, United States

Location

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, 47714, United States

Location

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, 46815, United States

Location

IN Onc/Hem Associates

Indianapolis, Indiana, 46202, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

St. Vincent Hospital & Health Centers

Indianapolis, Indiana, 46206, United States

Location

IU Health Arnett Cancer Center

Lafayette, Indiana, 47904, United States

Location

Horizon Oncology Researcg

Lafayette, Indiana, 47905, United States

Location

IU Health at Ball Memorial Hospital

Muncie, Indiana, 47303, United States

Location

Monroe Medical Associates

Munster, Indiana, 46321, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

Providence Medical Group

Terre Haute, Indiana, 47802, United States

Location

Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

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

Mount Holly, New Jersey, 08060, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Pennsylvania Oncology-Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Related Publications (1)

• 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)

  RESULT

Related Links

• Hoosier Oncology Group Home Page

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

Cisplatin; Etoposide; vandetanib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

The primary object analysis was under powered. The sample size calculation determined 34 subjects per arm, however the actual primary objective analysis was based on 31 subjects per arm.

Results Point of Contact

• Title: Georgia Gould
• Organization: Hoosier Cancer Research Network

ggould@hoosiercancer.org

317-921-2050

Study Officials

• Nasser Hanna, M.D.

  Hoosier Oncology Group, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 13, 2008
• Study Start: January 1, 2008
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 11, 2020
• Results First Posted: November 18, 2015

Record last verified: 2020-02

Locations

US (19)