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

NCT03754933 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: PNP-002R01FD005746-01A114271
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Recurrent Head and Neck Cancer

Keywords

Fludarabine; Adenovirus; Head & neck squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment.

  Safety measures evaluated by medical history, physical examination, vital signs, inspection of tumor site, performance status, EKG, chest X-ray (CXR), blood chemistry, hematology, CD4/CD8 T-cell counts, urinalysis, PT/PTT, blood sample for adenovirus, urine for adenovirus, F-Ade plasma level, blood sample for antibody against adenovirus, and monitoring adverse events.

  up to 7 months

Secondary Outcomes (5)

• Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1.

  up to 7 months

• Progression Free Survival (PFS) - Time From First Intratumoral Injection to Date of Progression or Death, Calculated in Months

  up to 7 months

• Probability of No Progressive Disease or Death and 95% CI Up to 6 Months (%)

  6 months

• Overall Survival (OS) - Time From First Intratumoral Injection to Date of Death up to 60 Days Post Last Injection

  up to 7 months

• Probability of No Death and 95% CI up to 1 Month and up to 6 Months

  6 months

Study Arms (1)

Ad/PNP + fludarabine phosphate, 5 cycles

EXPERIMENTAL

Ad/PNP + fludarabine phosphate, 5 cycles

Biological: Ad/PNP; Drug: Fludarabine Phosphate

Interventions

Ad/PNP BIOLOGICAL

Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase

Also known as: Gedeptin

Ad/PNP + fludarabine phosphate, 5 cycles

Fludarabine Phosphate DRUG

Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.

Also known as: Fludara

Ad/PNP + fludarabine phosphate, 5 cycles

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provided Informed Consent
• Age ≥ 18 years
• 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.
• 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)
• 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.
• Eastern Cooperative Oncology Group performance status of ≤ 2
• 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.
• Absolute neutrophil count ≥ 1,500 cells/ul; hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/ul
• Serum creatinine ≤ 1.5 mg/dl, or calculated creatinine clearance ≥ 60 ml/min
• 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
• Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 x upper limit of normal
• Activated partial thromboplastin (aPTT) time ≤ 1.5 x upper limit of normal
• 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)
• All patients of reproductive potential must agree to use a medically acceptable form of contraception (eg, hormonal birth control, double-barrier method) or abstinence.

You may not qualify if:

• Prior history or current diagnosis of leukemia
• Have received any gene therapy products or oncolytic viral therapy
• Receiving allopurinol
• Received an investigational drug within 30 days prior to first injection of Ad/PNP
• 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.)
• 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)
• Have significant baseline neuropathy (\> Grade 2 based on Common Terminology Criteria for Adverse events \[CTCAE\] v5.0)
• Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease, active infection)
• Had within 6 months prior to enrollment: Myocardial infarction, cerebral vascular accident, uncontrolled congestive heart failure, significant liver disease, unstable angina
• Fever (temperature \> 38.1 degrees C orally)
• 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.
• Receiving anticoagulants other than those to maintain patency of venous lines
• Women who are pregnant or breast feeding
• History of HIV infection. No requirement for testing.

Sponsors & Collaborators

• GeoVax, Inc.: lead
• Stanford University: collaborator
• Emory University: collaborator
• Thomas Jefferson University: collaborator

Study Sites (3)

Stanford University

Stanford, California, 94305, United States

Location

Winship Cancer Institute - Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (2)

• Parker WB, Sorscher EJ. Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors. Curr Pharm Des. 2017 Nov 8:10.2174/1381612823666171109101851. doi: 10.2174/1381612823666171109101851. Online ahead of print.

  PMID: 29119917 BACKGROUND

• Rosenthal EL, Chung TK, Parker WB, Allan PW, Clemons L, Lowman D, Hong J, Hunt FR, Richman J, Conry RM, Mannion K, Carroll WR, Nabell L, Sorscher EJ. Phase I dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors. Ann Oncol. 2015 Jul;26(7):1481-7. doi: 10.1093/annonc/mdv196. Epub 2015 Apr 21.

  PMID: 25899782 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Adenoviridae Infections; Squamous Cell Carcinoma of Head and Neck

Interventions

fludarabine phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; DNA Virus Infections; Virus Diseases; Infections; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Kelly T. McKee, Jr., MD, MPH
• Organization: GeoVax, Inc.

kmckee@geovax.com

(678) 384-7220

Study Officials

• A. Dimitrios Colevas, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: November 27, 2018
• Study Start: February 11, 2019
• Primary Completion: December 29, 2023
• Study Completion: December 31, 2024
• Last Updated: March 27, 2025
• Results First Posted: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)