Safety and Efficacy of Repeat Administration of Ad/PNP and Fludarabine Phosphate in Patients With Local Head/Neck Cancer

Trial ID or NCT#



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Primary Objective: The primary objective of the study is to evaluate the safety of repeat administration of a dose level of Ad/PNP plus fludarabine phosphate (F-araAMP) which demonstrated anti-tumor activity in patients with advanced head and neck cancer in a completed phase I study. Secondary Objective: The secondary objective is to evaluate the antitumor activity of repeat administration of Ad/PNP plus F-araAMP. FDA Office of Orphan Drugs Division is a source of funding for the overall project.

Official Title

Phase 1/2, Open-label Study Evaluating Safety of Repeat Administration of Ad/PNP-F-araAMP (Ad/PNP Administered Intratumorally Followed by Intravenous Fludarabine Phosphate) in Subjects With Recurrent, Local Head and Neck Cancer

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. 1. Provided Informed Consent 2. Age ≥ 18 years 3. Patients with histologically or cytologically confirmed diagnosis of recurrent cancer of the head and neck region for whom there is no curative treatment option. For the purposes of trial eligibility, cancers of the head and neck shall include, in addition to head and neck squamous cell carcinoma (HNSCC), cutaneous squamous cell primary sites and squamous cell carcinoma of unknown primary presenting with neck lymph nodal disease, as well as nasopharyngeal carcinoma, and salivary gland tumors. 4. All standard or approved treatment options that would provide substantive palliation must have failed, been exhausted, or patient not eligible or willing to use them (for example neuropathy, nephropathy , or hearing loss precluding the use of cisplatin) 5. Tumor mass (primary tumor and/or lymphadenopathy) measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and technically suitable for intratumoral injections (otolaryngologist will determine feasibility). Patients with nodal disease (or metastatic disease) that is needle accessible are eligible. Patients with additional tumors (including distant metastatic disease) beyond the intratumoral injection accessible tumor(s) that are not accessible for intratumoral injection are eligible ONLY if the patient has no other treatment option for the metastatic disease and treatment of local disease may provide the patient some benefit or palliation. 6. Eastern Cooperative Oncology Group performance status of ≤ 2 7. In the judgment of the Investigator, the patient has recovered sufficiently from any previous significant therapy side effects or toxicities prior to Ad/PNP administration. 8. Absolute neutrophil count ≥ 1,500 cells/ul; hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/ul 9. Serum creatinine ≤ 1.5 mg/dl, or calculated creatinine clearance ≥ 60 ml/min 10. Bilirubin ≤ upper limit of normal, alanine aminotransferase ≤ 1.5 x upper limit of normal and/or aspartate aminotransferase ≤ 1.5 x upper limit of normal, alkaline phosphatase ≤ 2.5 x upper limit of normal 11. Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 x upper limit of normal 12. Activated partial thromboplastin (aPTT) time ≤ 1.5 x upper limit of normal 13. Female patients must have a negative urine or serum pregnancy at screening (pregnancy test is not required for patients with bilateral oophorectomy and/or hysterectomy or for those patients who are > 1 year postmenopausal) 14. All patients of reproductive potential must agree to use a medically acceptable form of contraception (eg, hormonal birth control, double-barrier method) or abstinence.
Exclusion Criteria:
  1. 1. Prior history or current diagnosis of leukemia 2. Have received any gene therapy products or oncolytic viral therapy 3. Receiving allopurinol 4. Received an investigational drug within 30 days prior to first injection of Ad/PNP 5. Received radiation treatment < 4 weeks prior to first injection of Ad/PNP, and does not have any RECIST 1.1 evaluable lesions that are outside the radiation field. (If the patient has RECIST 1.1 evaluable lesions outside the radiation field then they can be included.) 6. Received chemotherapy (systemic anticancer treatment) < 4 weeks prior to first injection of Ad/PNP and has not recovered from all the related side effects. (If the patient has recovered from all related side effects or has reached a new baseline, then they may begin receiving treatment at sooner than 4 weeks) 7. Have significant baseline neuropathy (> Grade 2 based on Common Terminology Criteria for Adverse events [CTCAE] v5.0) 8. Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease, active infection) 9. Had within 6 months prior to enrollment: Myocardial infarction, cerebral vascular accident, uncontrolled congestive heart failure, significant liver disease, unstable angina 10. Fever (temperature > 38.1 degrees C orally) 11. Receiving chronic systemic corticosteroids (> 3 weeks) or any chronic immunosuppressive medications within 14 days prior to first injection of Ad/PNP. Subjects receiving short courses of corticosteroids are considered eligible for the study. 12. Receiving anticoagulants other than those to maintain patency of venous lines 13. Women who are pregnant or breast feeding 14. History of HIV infection. No requirement for testing.


A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD
Medical oncologist, Head and neck specialist, Cutaneous oncology specialist
Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)

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Head and Neck Team