Radiation Therapy (XRT) and ZD6474 in Non-Small Cell Lung Cancer (NSCLC)

NCT00745732 | Terminated Phase 1

• 2 other identifiers: 2003-0787NCI-2012-02225
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives:

• To assess the safety of oral therapy with ZD6474 by evaluating the frequency, severity, and duration of treatment-emergent adverse events in patients with poor prognosis lung cancer.
• To record the extent, frequency and duration of any tumor responses to this treatment regimen and assess whether ZD6474 augments the efficacy of radiation therapy in non-small cell lung cancer patients.
• To determine the recommended phase II dose of ZD6474 for future clinical studies with radiation therapy. Secondary Objectives:
• To determine the effects on metabolism and angiogenic factors by positron emission tomography (PET) scan/computed tomography (CT) scan , vascular endothelial growth factor (VEGF), and circulating endothelial cell levels in patients treated with ZD6474 and radiation therapy.

Conditions

Non-Small Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Lung Cancer; NSCLC; ZD6474; ZACTIMA; Vandetanib; Inoperable NSCLC; Unresectable NSCLC; Radiation Therapy; Palliative radiation therapy; Angiogenesis

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Weekly evaluations from baseline through 3 to 7 weeks of treatment (3-5 days per week for radiation and up to 3 doses tested)

Secondary Outcomes (1)

• Tumor Response

  Baseline to completion of radiation treatment (3-7 weeks), 1 and 3 months post treatment, every 3 months for 2 years, every 6 months for 3 years then annually

Study Arms (1)

Radiation Therapy + ZD6474

EXPERIMENTAL

Radiation Therapy - Phase I: 45 Gy at 3 Gy per fractions once a day. Phase II: 45 Gy at 3 Gy per fraction once a day or 66-70 Gy at 2 Gy per fraction once a day. ZD6474 (ZACTIMA) beginning at 100 mg once a day by mouth.

Drug: ZD6474 (ZACTIMA); Radiation: Radiation Therapy

Interventions

ZD6474 (ZACTIMA) DRUG

ZD6474 (ZACTIMA) beginning at 100 mg once a day by mouth

Also known as: Zactima, Vandetanib

Radiation Therapy + ZD6474

Radiation Therapy RADIATION

Phase I: 45 Gy at 3 Gy per fractions once a day. Phase II: 45 Gy at 3 Gy per fraction once a day or 66-70 Gy at 2 Gy per fraction once a day.

Also known as: Radiation, XRT

Radiation Therapy + ZD6474

Eligibility Criteria

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

You may qualify if:

• Non-small cell lung cancer patients Stage I-IV with surgically unresectable or medically inoperable tumors.
• Patients for whom radiation therapy alone is the recommended treatment, who are not candidates for other chemo-radiation protocols.
• For Phase I: Patients with any stage for whom palliative radiation therapy to 45 Gy/15 Fx is the recommended treatment (patients with obstructive pneumonia are eligible).
• The primary tumor and/or regional lymphatic metastases must be evaluable radiographically.
• Have at least one lesion greater than 2 cm in diameter measurable by CT.
• Age at least 18 years old.
• Karnofsky performance status \>/=50, weight loss \< 30% within the previous 6 months.
• No prior invasive malignancies less than or equal to 3 years prior to study entry and no prior radiation to the thorax.
• aspartate aminotransferase-alanine aminotransferase (AST/ALT) \< 2.5 upper limit of normal (ULN) or alk phos (ALP) \< 2.5 \* ULN, or \< 5\* ULN if judged by the investigator to be related to liver metastases
• Total bilirubin \< 1.5 \* ULN or \<3 \* ULN if related to liver metastases
• Serum creatinine \< 1.5 \* Upper Limit of the Reference Range (ULRR) or creatinine clearance greater than or equal to 50 mL/minute (calculated by Cockcroft-Gault formula.)
• White blood count (WBC) \> 3000/mm3, serum hemoglobin \>/= 8 gm/dl, platelet count \>/= 100,000/mm3, absolute granulocyte count \>/= 2,000.
• international normalized ratio (INR) within normal laboratory value range and prothrombin time (PT) and partial thromboplastin time (PTT) within 3 seconds of normal range.
• Potassium must be within normal laboratory value range. Serum calcium and magnesium must be within normal range. Supplementation may be used to normalize.
• Patients with distant metastases and life expectancy greater than or equal to 3 months are eligible.

You may not qualify if:

• Pregnancy or breast feeding
• Bronchoalveolar carcinoma
• Oxygen saturation less than 90% on room air or requirement for oxygen supplementation
• Any condition that is likely to interfere with regular follow-up
• Patient cannot have participated in any clinical trial involving conventional or investigational drugs within 4 weeks prior to administration of ZD6474
• Patient cannot have received radiation therapy or chemotherapy within 4 weeks prior to administration of ZD6474 (6 weeks for nitrosoureas and mitomycin)
• Patient cannot be receiving herbal remedies or other over-the-counter biologics (e.g., shark cartilage)
• Patient cannot be receiving drugs with known significant 3A4 inhibitory effects (e.g., ketoconazole, erythromycin, and verapamil)
• Patient cannot be receiving drugs with known corneal toxicology (e.g., tamoxifen, chlorpromazine, amiodarone, and chloroquine)
• Patients cannot have received previous treatment with agents that block the EGF or VEGF pathways
• Patient cannot have serum calcium levels below the lower limits of normal.
• Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease \>/=2 (see Appendix J) within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events (CTCAE) grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• QTc with Bazett's correction that is unmeasurable, or \>/= 480 msec on screening Electrocardiograph (ECG/EKG). If a patient has QTc \>/= 480 msec on screening EKG, the screening EKG may be repeated twice (at least 24 hours apart). The average QTc from the three screening EKGs must be \<480 msec in order for the patient to be eligible for the study.
• Patients cannot have a history of QT prolongation with other medication

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center Official Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

vandetanib; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• Melenda D. Jeter, MD, MPH

  Assistant Professor, UT MDACC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2008
• First Posted: September 3, 2008
• Study Start: October 9, 2008
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 14, 2018

Record last verified: 2018-11

Locations

US (1)