• To assess the response rate of ABT-510 (thrombospondin) in patients with advanced head and neck cancer [ Time Frame: Radiologic Assessment after every 2 cycles ] [ Designated as safety issue: No ]
  
• To investigate the effect on endothelial cell apoptosis by ABT-510 (thrombospondin) in advanced head and neck cancer patient [ Time Frame: baseline, day 28 (pre-dose),at week 8 (pre-dose), and at final visit. ] [ Designated as safety issue: No ]
  

• To describe the effect of ABT-510 (thrombospondin) on downstream biologic targets including VEGF-R, p53 and apoptosis [ Time Frame: baseline, day 28 (pre-dose), at week 8 (pre-dose), and at final visit. ] [ Designated as safety issue: No ]
  
• To assess the pharmacokinetic/pharmacodynamic profile of ABT-510 (thrombospondin) in advanced head and neck cancer patients [ Time Frame: baseline, day 28 (pre-dose), at week 8 (pre-dose), and at final visit. ] [ Designated as safety issue: No ]
  
• To assess the imaging characteristics of ABT-510 (thrombospondin) in advanced head and neck cancer patients [ Time Frame: Radiologic assessment following every 2 cycles ] [ Designated as safety issue: No ]
  
• To assess the toxicity and tolerability of ABT-510 (thrombospondin) [ Time Frame: Routine PE weekly during the first 4 weeks, at day 56, at end of study. ] [ Designated as safety issue: No ]
  

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.

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.