The goals of this clinical research study are to see how individuals with advanced head and neck cancer respond to treatment with the new drug thrombospondin (ABT-510) and to learn how effective it is in destroying cancer cells. The safety of ABT-510 and the effect ABT-510 has on cells in the body will also be studied.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: ABT-510 (thrombospondin)	Phase I Phase II

Further Study Details: 

Primary Outcomes: To assess the response rate of ABT-510 (thrombospondin) in patients with advanced head and neck cancer; To investigate the effect on endothelial cell apoptosis by ABT-510 (thrombospondin) in advanced head and neck cancer patient
Secondary Outcomes: To describe the effect of ABT-510 (thrombospondin) on downstream biologic targets including VEGF-R, p53 and apoptosis; To assess the pharmacokinetic/pharmacodynamic profile of ABT-510 (thrombospondin) in advanced head and neck cancer patients; To assess the imaging characteristics of ABT-510 (thrombospondin) in advanced head and neck cancer patients; To assess the toxicity and tolerability of ABT-510 (thrombospondin)
Expected Total Enrollment:  37

This is a phase Ib/II, single-center, open-label study designed to assess the safety, tolerability, pharmacokinetics, and biologic efficacy of ABT-510 (thrombospondin). Participants will be patients with incurable head and neck cancer.

Patients will begin at a fixed dose level of thrombospondin subcutaneously twice daily. Cycles of treatment are 28 days (4 weeks). Patients will be treated with thrombospondin until progression of tumor or toxicity.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Patient has histologically proven squamous cell carcinoma of the head and neck that is not amenable to curative therapy, including radiation or surgery (including surgery following induction chemotherapy or chemo-radiation).
• Patient’s tumor is biopsy accessible.
• Patient has a Karnofsky performance status >/= 70.
• Patient has adequate bone marrow function: WBC >/= 3,000 cells/mm3, ANC >/= 1,500 cells/mm3, platelet count >/= 100,000 cells/mm3, Hgb >/= 9.0 g/dL.
• Patient has adequate liver function: total bilirubin level </= 2.0 mg/dL, albumin >/= 2.5 g/dL.
• Transaminases (SGOT and/or SGPT) may be up to 2.5 x ULN if alkaline phosphatase is </= ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are </= ULN. However, patients who have both transaminase elevation > 1.5 x ULN and alkaline phosphatase > 2.5 x ULN are not eligible for this study.
• Patient has serum creatinine < 2 mg/dl
• Patient has signed a written informed consent.
• Patient may have received any number of prior chemotherapeutic regimens for recurrent or metastatic disease.
• The subject must not be pregnant or breastfeeding. All subjects (male and female) should practice contraception (e.g., barrier, hormonal, intrauterine device [IUD]) or abstain from sexual intercourse while in the study and for up to two months following completion of therapy.
• The subject is able to self-administer or has a caregiver who can reliably administer subcutaneous (SC) injections.
• Patient >/= 18 years of age.

Exclusion Criteria:

• No biopsy accessible tissue.
• Patient has received prior radiation therapy to biopsy site within the past 3 months. (Patient may have received palliative radiation within the past 2 weeks, but not to the biopsy site.)
• Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient’s understanding of the informed consent.
• Patient requires total parenteral nutrition with lipids.
• Patient has a history of uncontrolled heart disease including congestive heart failure, angina at rest, myocardial infarct in the last 6 months, uncontrolled hypertension with systolic blood pressure (BP) >160 or diastolic BP >90, systolic BP <90 or symptomatic hypotension, or symptomatic or potentially life-threatening tachycardia, bradycardia or arrhythmia.
• Pregnant women and women who are currently breast-feeding may not participate in this study. All women of childbearing potential must have a negative pregnancy test within 24 hours prior to enrolling in the study.
• Serious infection or other intercurrent illness requiring immediate therapy.
• The subject has a history of or currently exhibits clinically significant cancer related events of bleeding (e.g., hemoptysis). The subject has a recent history of (within 4 weeks from Study Day 1) or currently exhibits other clinically significant events of bleeding.
• If subject is receiving therapeutic anticoagulation therapy, low dose anticoagulation for catheter prophylaxis will be permitted; PT/PTT must be within normal limits.
• The patient has a history of or currently exhibits central nervous system (CNS) metastasis. Brain magnetic resonance imaging (MRI) within 28 days of enrollment is required to confirm the absence of CNS metastases.
• Patient has received chemotherapy or biologic therapy within 3 weeks of registration.

Please refer to this study by ClinicalTrials.gov identifier  NCT00113334

Louise Christmas, RN      713-745-6760    lchristmas@mdanderson.org

Texas
      University of Texas MD Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting

Study chairs or principal investigators

Edward S. Kim, MD,  Principal Investigator,  M.D. Anderson Cancer Center   

Study ID Numbers:  2003-1027
Record last reviewed:  June 2005
Last Updated:  June 30, 2005
Record first received:  June 7, 2005
ClinicalTrials.gov Identifier:  NCT00113334
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-05