Study of ABT-510 (Thrombospondin Analogue) in Patients With Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1b/2 Study of ABT-510 (Thrombospondin Analogue) in Patients With Advanced Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: ABT-510


Participation Criteria
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Eligibility Criteria
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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: White blood count (WBC) >/= 3,000 cells/mm3, absolute neutrophil count (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 * upper limit of normal (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 * ULN and alkaline phosphatase > 2.5 * 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 blood pressure (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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-510 (Thrombospondin)<br>Fixed dose level of thrombospondin 100 mg subcutaneously twice daily. | Drug: ABT-510<br>* 100 mg subcutaneously twice daily<br>* Other names: Thrombospondin Analogue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response rate defined as percentage of number of complete response or partial response in total number of participants treated. Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): >20% increase in sum LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1/> new lesions; Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD, reference smallest sum LD. Trial conducted by Simon's optimal two-stage design and response rate estimated accordingly. For status of PR or CR, changes in tumor measurements confirmed by repeat assessments performed at 6 weeks, no less than 4 weeks after criteria for response is first met. | Baseline to 6 weeks for PR or CR response assessment (minimal 4 week cycle + assessments). Overall study period 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Thrombospondin Analogue, ABT-510, Antiangiogenic agent, Lung, Skin, Thyroid