Vandetanib, Carboplatin, and Paclitaxel in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer That Can Be Removed by Surgery

This study has been terminated.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Shirish Gadgeel, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00459121
First received: April 9, 2007
Last updated: April 3, 2013
Last verified: February 2013
  Purpose

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving vandetanib together with carboplatin and paclitaxel works in treating patients with stage I, stage II, or stage III non-small cell lung cancer that can be removed by surgery.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: paclitaxel
Drug: Zactima
Procedure: neoadjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Assessment of Feasibility and Safety of the Addition of ZD6474 (Zactima) to Carboplatin and Paclitaxel Administered Neo-Adjuvantly in Stage IB, II and T3, N1 Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Complete Resection (R0) Rate [ Time Frame: Following three cycles of pre-operative zactima and carboplatin/paclitaxel ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Post-Operative Mortality Rate [ Time Frame: at 30 days ] [ Designated as safety issue: No ]
  • Assess Toxicity of This Regimen and the Percentage of Patients Completing All Planned Cycles of Therapy [ Time Frame: Weekly for the first cycle; Thereafter within 72 hours of each dose of carboplatin/paclitaxel ] [ Designated as safety issue: Yes ]
    Serum chemistry includes Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total protein, SGOT [AST], SGPT [ALT], sodium, laboratory tests should be done on a weekly basis for the first cycle. After the first cycle laboratory tests should be done within 72 hours of each dose of carboplatin/paclitaxel.

  • Assess the Clinical Response Rate of the Proposed Pre-operative Regimen [ Time Frame: End of three cycles of treatment ] [ Designated as safety issue: Yes ]
    Patients will undergo tumor evaluation when all of the three cycles have been completed unless the treating physician has concerns regarding tumor progression. If the patient has undergone tumor evaluation prior to the last cycle the patient will require repeat tumor assessment within 4 weeks of completion of the last cycle of therapy

  • Assess the Complete Pathologic Complete Response (CR) Rate With This Regimen. [ Time Frame: 30 days post surgery ] [ Designated as safety issue: No ]
    Evaluation of the number of patients who have no evidence of tumor in the resected tumor.


Enrollment: 2
Study Start Date: July 2007
Study Completion Date: October 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zactima, Paclitaxel, Carboplatin

Zactima- 100 mg orally daily, starting on day 1 of cycle 1. Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1. Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1 Duration of each cycle: 21 days. The last dose of zactima will be on the first day of the last cycle.

Neoadjuvant Surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.

Drug: carboplatin
Carboplatin AUC6 IV, every 3 weeks starting on day 1 of cycle 1
Other Name: Paraplatin ®
Drug: paclitaxel
Paclitaxel- 200mg/m2 IV, every 3 weeks starting on day 1 of cycle 1.
Other Names:
  • Taxol ®
  • Onxal TM
Drug: Zactima
Zactima- 100 mg orally daily, starting on day 1 of cycle 1.
Other Names:
  • Caprelsa
  • ZD6474
  • Vandetanib
Procedure: neoadjuvant therapy
Neoadjuvant surgery: Surgical resection of the tumor will be performed after the resolution of all the adverse effects from the last cycle of treatment but no earlier than 3 weeks after the last cycle of treatment.
Other Name: R0 Resection

Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility of neoadjuvant vandetanib in combination with carboplatin and paclitaxel in patients with resectable stage IB, II, or IIIA non-small cell lung cancer.

Secondary

  • Assess the 30-day postoperative mortality rate in these patients.
  • Assess the toxicity of this regimen in these patients.
  • Determine the percentage of patients who complete all planned courses of therapy.
  • Assess the clinical response rate in patients treated with this regimen.
  • Assess the pathologic complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral vandetanib once daily on days 1-21. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 3 courses.

Patients undergo surgery at least 3 weeks after the last course of chemotherapy.

PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria:

    • Stage IB or II disease
    • T3, N0-1 disease (stage IIIA)
  • Deemed a surgical candidate
  • No prior lung cancer (NSCLC or small cell lung cancer)

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No evidence of severe or uncontrolled systemic disease or any concurrent condition that, in the opinion of the investigator, would preclude study compliance
  • No peripheral neuropathy ≥ grade 2
  • No hemoptysis within the past 12 weeks
  • No spontaneous bleeding within the past 12 weeks
  • No clinically significant cardiac event (e.g., NYHA class II-IV heart disease, myocardial infarction) within the past 3 months
  • No history of asymptomatic sustained ventricular tachycardia or arrhythmia that is symptomatic or requires treatment, including any of the following:

    • Multifocal premature ventricular contractions
    • Bigeminy
    • Trigeminy
    • Ventricular tachycardia
    • Uncontrolled atrial fibrillation

      • Atrial fibrillation controlled with medication allowed
  • No history of QTc prolongation as a result from other medication that required discontinuation of that medication
  • No congenital long QT syndrome or first-degree family relative with an unexplained death before the age of 40
  • No left bundle branch block
  • No QTc with Bazett's correction that is unmeasurable or QTc ≥ 480 milliseconds on screening ECG

    • Patients with QTc ≥ 480 milliseconds on screening ECG may have ECG repeated twice

      • Average QTc from the 3 screening ECG's must be < 480 milliseconds
  • No uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg)
  • No active diarrhea or active gastrointestinal disease that may affect the absorption of study drugs or ability to tolerate study drugs
  • No other malignancy within the past 3 years except in situ cervical carcinoma or adequately treated basal cell or squamous cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

  • More than 4 weeks since major surgery and recovered
  • No prior carboplatin, paclitaxel, or vandetanib
  • More than 30 days since prior investigational agents
  • More than 2 weeks since prior and no concurrent drugs that induce CYP3A4 including, but not limited to, any of the following:

    • Rifampin
    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Hypericum perforatum (St. John's wort)
  • No medication that may cause QTc prolongation or induce torsades de pointes for 2 weeks prior to beginning study treatment, during, and for 2 weeks after completion of study treatment
  • No concurrent combination antiretroviral treatment for HIV-positive patients
  • No other concurrent investigational agents
  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: NCT00459121

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Shirish M. Gadgeel, MD Barbara Ann Karmanos Cancer Institute
  More Information

No publications provided

Responsible Party: Shirish Gadgeel, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00459121     History of Changes
Other Study ID Numbers: CDR0000539273, P30CA022453, WSU-2006-122, WSU-011807MP2F, WSU-0612004427, ZENECA-IRUSZACT0029
Study First Received: April 9, 2007
Results First Received: November 12, 2012
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014