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.
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.
- 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.
- 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.