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


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Trial ID: NCT03754933,


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

Stanford Investigator(s)

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   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

   8. Absolute neutrophil count ≥ 1,500 cells/ul; hemoglobin ≥ 9 g/dl, platelets ≥

   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

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. 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

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

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.


biological: Ad/PNP

drug: Fludarabine Phosphate


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Head and Neck Team

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