MDACC Study Summary 2006-0492

Study Summary
No. 2006-0492:.......Head And Neck......Vali Papadimitrakopoulou......Thoracic and Head and Neck Med

Study Summary Title



Study Summary Number:	2006-0492

Study Title:	An Open Label, Multi-Center, Phase I Study To Assess The Maximum Tolerated Dose of ZD6474 (ZACTIMA) Given Concomitantly with Radiation Therapy or Concomitantly with Weekly Cisplatin Chemotherapy and Radiation Therapy in Patients with Previously Untreated, Unresected, Stage III-IV Head and Neck Squamous Cell Carcinoma

Physician

New Patient Referral



Name:	Vali Papadimitrakopoulou	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Thoracic and Head and Neck Med	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6363 Contact us about clinical trials

General Information



Disease Group:	Head And Neck	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Pts will return on a wkly basis (beginning each wk) during study treatment. FU, pts will be seen 30 & 60 days post dose last dose and again 90 days post last dose and q3 mos thereafter until the end of 2 yrs post-active treatment FU.

Treatment Agents:	Cisplatin Radiation ZD6474	Home Care:	N/A

Treatment Loc:	Independent Multicenter Arrangements

Estimated Length of Stay in Houston:	The protocol is performed on an outpatient basis.


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

Primary Objective:

Determine the safety profile, tolerability and (MTD) of ZD6474 in combination with radiation therapy (RT) and ZD6474 in combination with RT and cisplatin chemo, for approx 8-9 wks of study therapy, in pts with previously untreated, unresected, stage III-IV head and neck squamous cell carcinoma (HNSCC).

Secondary Objectives:

Define the objective tumor response rates (ORR), disease control rate (DCR), and locoregional control rates (LRCR) per Response Evaluation Criteria in Solid Tumors (RECIST).
Assess rate of locoregional recurrence (LRR) and distant disease recurrence at 2 years.
Assess progression-free survival (PFS) and duration of locoregional control.
Investigate whether there is any change in the steady state exposure to ZD6474 due to RT or RT + cisplatin or the method of administration
Investigate whether there is any change in the exposure to cisplatin due to ZD6474 as assessed by total platinum.

Exploratory Objectives:

Investigate the correlation between EGFR gene amplification, EGFR protein expression, vimentin protein expression, E-cadherin protein expression, and ZD6474 efficacy and toxicity in pre-treatment tumor samples from those pts where such tumor material is available.
Investigate the correlation between inhibition of EGFR and VEGFR signalling pathways, tumor cell and endothelial cell apoptosis, tumor microvessel density, and ZD6474 dose, efficacy and toxicity in pre-treatment and on-treatment tumor samples from those pts where such tumor material is available.
Investigate the correlation between markers of tumor hypoxia (hypoxia inducible factor [HIF}, VEGF) and ZD6474 dose, efficacy and toxicity in pre-treatment and on-treatment tumor samples from those pts where such tumor material is available.
Investigate the correlation between changes in gene and protein expression, and ZD6474 dose, efficacy and toxicity in pre-treatment and on-treatment tumor samples from those pts where such tumor material is available.

Study Status Information



Study Activation / Registration Date:	11/21/2006

IRB Review and Approval Date:	10/04/2006

Study Type:	Phase I

Recruitment Status:	Closed

Projected Accrual:	48

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Provision of informed consent.

2) Female or male aged 18 years and over

3) Histologically or cytologically confirmed (from the primary lesion and/or lymph nodes) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx that has not been previously treated or resected.

4) Stage III to IV disease, with no proven hematogenous metastatic disease.

5) WHO performance status of 0-1

6) One or more measurable lesion at least 10 mm in the longest diameter by spiral CT scan or 20 mm with conventional techniques (according to RECIST guidelines)

7) Patients with history of non-melanoma skin cancer, or previous malignancies treated at 3 years prior to the current tumor from which the patient has remained continually disease-free and patients with in situ carcinoma of the cervix and adequately treated basal cell or squamous cell carcinoma of the skin are eligible

8) Life expectancy of >/= 12 weeks

9) Negative pregnancy test for women of childbearing potential

Exclusion Criteria:

1) Presence of simultaneous primary tumors

2) Women who are currently breast-feeding

3) Men or women unwilling to use an acceptable method of contraception while on study

4) Major surgery within 4 weeks, or incompletely healed surgical incision

5) Any concomitant medications that may affect QTc or induce CYP3A4 function and cannot be discontinued. Drugs listed in Appendix E, Table 2, that in the Investigator's opinion cannot be discontinued, are allowed (additional criteria must also be met – see Exclusion Criteria #15)

6) Any previous anti-cancer therapy given for treatment of current diagnosis

7) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase > 2.5 x ULRR

8) Serum bilirubin > ULRR

9) Creatinine clearance </= 30 mL/minute (calculated by Cockcroft-Gault formula). Note for the cisplatin-containing regimen, patients with cratinine clearance </= 60 mL/minute are excluded.

10) Significant cardiac event (eg. myocardial infarction, super vena cava (SVC) syndrome), within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia

11) History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia or uncontrolled atrial fibriallation), which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation controlled on medication permitted

12) Congenital long QT syndrome or a 1st degree relative with an unexplained sudden death under 40 years of age (except for Sudden Infant Death Syndrome)

13) QT prolongation with other medications that required discontinuation of that medication

14) Presence of left bundle branch block (LBBB).

15) QTc with Bazett's correction unmeasurable or >/= 480 msec on screening ECG (Note: If a patient has QTc interval >/= 480 msec on the screening ECG, two additional ECGs should be done [at least 24 hours apart]. The average QTc from the three screening ECGs must be </= 480 msec in order for the patient to be eligible for the study). Patients who are receiving a drug that has a risk of QTc prolongation (See Appendix E, Table 2 in protocol) are excluded if the average of the screening QTc is >/= 460 msec

16) Potassium <4.0 mEq/L; serum calcium (ionized or adjusted for albumin), or magnesium out of normal range despite supplementation

17) Hypertension not controlled by medical therapy (systolic blood pressure greater than 140 millimeter of mercury mmHg or diastolic blood pressure greater than 90mm Hg)

18) Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol

19) Participation in an investigational study, or receipt of an investigational drug, within the past 30 days and during study.

20) Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational site)

21) Previous enrollment in the present study

22) Exclusion Criteria (applicable to Treatment Regimen 2 only) Any of the following is regarded as a criterion for exclusion from the study for patients who are assigned to receive cisplatin chemotherapy

23) Pre-existing neuropathy CTCAE grade 2 or worse

24) Known severe hypersensitivity to cisplatin or any of the excipients of the product

25) Evidence of pre-existing moderate to severe decline of hearing capacity

26) Neutrophils < 1.5 x 10^9/L or platelets < 100 x 10^9/L

27) Creatinine clearance </= 60 mL/minute (calculated by Cockcroft-Gault formula)

Links

Registration Number: NCT00450138
Study Information on Clinical Trials Registry (clinicaltrials.gov)