Recurrent Head and Neck CancerPhase 1/2NCT03754933
Safety and Efficacy of Repeat Administration of Ad/PNP and Fludarabine Phosphate in Patients With Local Head/Neck Cancer
A Phase 1/2 study testing Ad/PNP and Fludarabine Phosphate in people with Recurrent Head and Neck Cancer, run by GeoVax, Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Head and Neck Cancer
- What is being tested?
- Ad/PNP and Fludarabine Phosphate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesUnited States
- Study dates
- 11 Feb 2019to 31 Dec 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Winship Cancer Institute - Emory University School of Medicine
Atlanta, Georgia, 30322
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Stanford University
Stanford, California, 94305
About this study
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
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.
Read the detailed description
- Mechanism of action. The study drug, Ad/PNP-F-araAMP (Fludarabine phosphate) consists of a nonreplicating adenoviral vector expressing the E. coli purine nucleoside phosphorylase (PNP) injected intratumorally followed by intravenous administration of F-araAMP. This combination generates 2-fluoroadenine (F-Ade) within the tumor resulting in focal chemotherapeutic activity. F-araAMP is an agent that is rapidly cleaved by plasma phosphatases to fludarabine, which is the primary circulating form of the drug and has activity against certain hematological malignancies, but not against solid tumors such as head and neck squamous cell carcinoma (HNSCC). Fludarabine (F-araA) is an adenosine analog and substrate for E. coli PNP, which cleaves the glycosidic bond of F-araA to generate F-Ade. The F-Ade metabolite has shown pronounced activity against human tumor xenografts in mice. Many refractory tumors are refractory precisely because they have a very low growth fraction, i.e., a relatively small percentage of tumor cells dividing at any particular point in time. In nonclinical studies, significant in vivo antitumor activity has been demonstrated by F-Ade generation from F-araAMP in tumors in which 2.5 to 10% of cells express the E. coli PNP gene. In addition, anti-tumor effect was seen in patients with advanced solid tumors (melanoma and head and neck cancer) in the higher dose cohorts during a Phase 1 study (see next section).
- Tumor response with Ad/PNP-F-araAMP in Phase 1 Study. The safety and efficacy of Ad/PNP-F-araAMP has been evaluated in a Phase 1 study, PNP-001 (NCT01310179). Four escalating dose levels were evaluated in 10 subjects with head and neck cancer and 2 subjects with melanoma; clinical activity was observed at the highest dose levels following 3 intratumoral injections of Ad/PNP over 2 days and IV F-araAMP phosphate over 3 days. The overall response rate (CR+PR) was approximately 67% in the 2 highest dose cohorts, Cohorts 3 and 4. Results suggest a dose response effect. The duration of response in the injected tumor was limited, with 4 of 5 responding tumors having disease progression of the injected lesion prior to last follow-up on Day 56, suggesting that repeat administration should be evaluated. Ad/PNP + F-araAMP was well tolerated. No subject experienced a dose-limiting toxicity and none of the subjects discontinued study treatment. Overall, the activity and safety profile of Ad/PNP seen in the Phase 1 study supports further clinical evaluation of repeat administration of Ad/PNP (IT) and F-araAMP phosphate infusion for patients with HNSCC.
- Purpose of the Study. Based upon the tumor response seen with a single administration of the two highest dose levels of Ad/PNP-F-araAMP in the Phase 1 study (NCT01310179), PNP plans to investigate the safety and assess anti-tumor activity of repeat cycles of injection of Ad/PNP + F-araAMP in patients with advanced head and neck cancer. Subjects in the study will have RECIST 1.1 measurable HNSCC which is amenable to local injection for which there is no effective curative or palliative treatment option. This study population was selected since results from this Phase 1/2 trial are intended to support the safety of repeat dosing in further clinical investigation.
- Study Design. The trial is designed as a single-arm study to evaluate the safety of repeat cycles of Ad/PNP and F-araAMP in patients with recurrent HNSCC with tumor(s) accessible for injection. Ad/PNP will be injected intratumorally twice on Day 1 and once on Day 2 followed by infusion of F-araAMP daily on Days 3, 4, and 5. Subjects will receive repeat administration of Ad/PNP-F-araAMP every 4 weeks (i.e., each cycle) for 5 cycles or until injected tumor progresses, unacceptable toxicity occurs, no tumor is present for injection, or patient death. Tumor response in the injected tumor(s) will be assessed by physical examination as well as by radiographic imaging. All subjects will be monitored for adverse events during study participation.
- Conditions
- Recurrent Head and Neck Cancer
- Being tested
- Ad/PNP, Fludarabine Phosphate
- Keywords
- Fludarabine, Adenovirus, Head & neck squamous cell carcinoma
- Medical subject headings
- Head and Neck Neoplasms, Adenoviridae Infections, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad/PNPBiological
Also called Gedeptin
Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase
Also called Fludara
Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
| Study group | Role | What they receive |
|---|---|---|
| Ad/PNP + fludarabine phosphate, 5 cycles | Experimental | Ad/PNP + fludarabine phosphate, 5 cycles Receives: Biological: Ad/PNP; Drug: Fludarabine Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 7 months
Secondary outcomes (5)
Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1.
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: up to 7 months
Progression Free Survival (PFS) - Time From First Intratumoral Injection to Date of Progression or Death, Calculated in Months
Time to Event (Progression or Death) was defined as time from first intratumoral injection to date of progression or death for any cause, whichever occurred first, and was calculated, in months, as: (Date of first PD (Progressive Disease) or death or censoring - date of first intratumoral injection + 1) / 30.4375. PD was defined, based on the protocol-defined criteria for response in For-Injection tumors, as at least a 20% increase in the longest diameter (LD) of the injected lesions, taking as reference the smallest LD recorded on study (this includes the baseline LD if that is the smallest on study; note: appearance of one or more new lesions was considered progression in assessing overall tumor response.). PFS derivation did not include tumor assessments collected after the end of study treatment as these were not planned for collection beyond the final cycle.
Measured: up to 7 months
Probability of No Progressive Disease or Death and 95% CI Up to 6 Months (%)
Time to PD or death was defined as time from the first intratumoral injection to date of progression or death for any cause, whichever occurs first, and was calculated, in months, as: (Date of first PD or death or censoring - date of first intratumoral injection + 1) / 30.4375.
Measured: 6 months
Overall Survival (OS) - Time From First Intratumoral Injection to Date of Death up to 60 Days Post Last Injection
Time to death was defined as time from the first intratumoral injection to date of death for any cause, and was calculated, in months, as: (Date of death or censoring - date of the first intratumoral injection + 1) / 30.4375. Subjects still alive as of the data cut-off date were censored on the last known alive date from mortality status follow up. For subjects that were lost to follow up, the last visit in the database or last contact date where the subject was documented to be alive was used to estimate last known date alive.
Measured: up to 7 months
Probability of No Death and 95% CI up to 1 Month and up to 6 Months
Time to death was defined as time from the first intratumoral injection to date of death for any cause, and was calculated, in months, as: Date of death or censoring - date of the first intratumoral injection + 1 / 30.4375.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2018
- Study start11 Feb 2019
- Primary completion29 Dec 2023
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Recurrent Head and Neck CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- GeoVax, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Stanford University, Emory University, Thomas Jefferson University
- Responsible party
- Sponsor
- Investigators
- A. Dimitrios Colevas, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03754933
- Sponsor's protocol ID
- PNP-002
- Other IDs
- R01FD005746-01A1, 14271
- Status last verified
- Mar 2025
- First submitted
- 19 Oct 2018
- Last updated
- 27 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Parker WB, Sorscher EJ. Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors. Curr Pharm Des. 2017;23(45):7003-7024. doi: 10.2174/1381612823666171109101851.
PubMed 29119917Rosenthal 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.
PubMed 25899782
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03754933
- Acronym / sponsor ID
- PNP-002
- Conditions
- Recurrent Head and Neck Cancer
- Keywords
- Fludarabine, Adenovirus, Head & neck squamous cell carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- GeoVax, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Stanford University, Emory University, Thomas Jefferson University
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 29 Dec 2023 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 27 Nov 2018 (actual)
- Results
- Posted 20 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Mechanism of action. The study drug, Ad/PNP-F-araAMP (Fludarabine phosphate) consists of a nonreplicating adenoviral vector expressing the E. coli purine nucleoside phosphorylase (PNP) injected intratumorally followed by intravenous administration of F-araAMP. This combination generates 2-fluoroadenine (F-Ade) within the tumor resulting in focal chemotherapeutic activity. F-araAMP is an agent that is rapidly cleaved by plasma phosphatases to fludarabine, which is the primary circulating form of the drug and has activity against certain hematological malignancies, but not against solid tumors such as head and neck squamous cell carcinoma (HNSCC). Fludarabine (F-araA) is an adenosine analog and substrate for E. coli PNP, which cleaves the glycosidic bond of F-araA to generate F-Ade. The F-Ade metabolite has shown pronounced activity against human tumor xenografts in mice. Many refractory tumors are refractory precisely because they have a very low growth fraction, i.e., a relatively small percentage of tumor cells dividing at any particular point in time. In nonclinical studies, significant in vivo antitumor activity has been demonstrated by F-Ade generation from F-araAMP in tumors in which 2.5 to 10% of cells express the E. coli PNP gene. In addition, anti-tumor effect was seen in patients with advanced solid tumors (melanoma and head and neck cancer) in the higher dose cohorts during a Phase 1 study (see next section).
- Tumor response with Ad/PNP-F-araAMP in Phase 1 Study. The safety and efficacy of Ad/PNP-F-araAMP has been evaluated in a Phase 1 study, PNP-001 (NCT01310179). Four escalating dose levels were evaluated in 10 subjects with head and neck cancer and 2 subjects with melanoma; clinical activity was observed at the highest dose levels following 3 intratumoral injections of Ad/PNP over 2 days and IV F-araAMP phosphate over 3 days. The overall response rate (CR+PR) was approximately 67% in the 2 highest dose cohorts, Cohorts 3 and 4. Results suggest a dose response effect. The duration of response in the injected tumor was limited, with 4 of 5 responding tumors having disease progression of the injected lesion prior to last follow-up on Day 56, suggesting that repeat administration should be evaluated. Ad/PNP + F-araAMP was well tolerated. No subject experienced a dose-limiting toxicity and none of the subjects discontinued study treatment. Overall, the activity and safety profile of Ad/PNP seen in the Phase 1 study supports further clinical evaluation of repeat administration of Ad/PNP (IT) and F-araAMP phosphate infusion for patients with HNSCC.
- Purpose of the Study. Based upon the tumor response seen with a single administration of the two highest dose levels of Ad/PNP-F-araAMP in the Phase 1 study (NCT01310179), PNP plans to investigate the safety and assess anti-tumor activity of repeat cycles of injection of Ad/PNP + F-araAMP in patients with advanced head and neck cancer. Subjects in the study will have RECIST 1.1 measurable HNSCC which is amenable to local injection for which there is no effective curative or palliative treatment option. This study population was selected since results from this Phase 1/2 trial are intended to support the safety of repeat dosing in further clinical investigation.
- Study Design. The trial is designed as a single-arm study to evaluate the safety of repeat cycles of Ad/PNP and F-araAMP in patients with recurrent HNSCC with tumor(s) accessible for injection. Ad/PNP will be injected intratumorally twice on Day 1 and once on Day 2 followed by infusion of F-araAMP daily on Days 3, 4, and 5. Subjects will receive repeat administration of Ad/PNP-F-araAMP every 4 weeks (i.e., each cycle) for 5 cycles or until injected tumor progresses, unacceptable toxicity occurs, no tumor is present for injection, or patient death. Tumor response in the injected tumor(s) will be assessed by physical examination as well as by radiographic imaging. All subjects will be monitored for adverse events during study participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ad/PNP + fludarabine phosphate, 5 cycles | Experimental | Biological: Ad/PNP, Drug: Fludarabine PhosphateAd/PNP + fludarabine phosphate, 5 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ad/PNPAlso: GedeptinAd/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase | Biological | Ad/PNP + fludarabine phosphate, 5 cycles |
| Fludarabine PhosphateAlso: FludaraFludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia. | Drug | Ad/PNP + fludarabine phosphate, 5 cycles |
Primary outcome
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment.
Time frame: up to 7 months
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.
5 secondary outcomes
Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1.
Time frame: up to 7 months
Progression Free Survival (PFS) - Time From First Intratumoral Injection to Date of Progression or Death, Calculated in Months
Time frame: up to 7 months
Probability of No Progressive Disease or Death and 95% CI Up to 6 Months (%)
Time frame: 6 months
Overall Survival (OS) - Time From First Intratumoral Injection to Date of Death up to 60 Days Post Last Injection
Time frame: up to 7 months
Probability of No Death and 95% CI up to 1 Month and up to 6 Months
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29119917Parker WB, Sorscher EJ. Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors. Curr Pharm Des. 2017;23(45):7003-7024. doi: 10.2174/1381612823666171109101851.
- Background: PubMed 25899782Rosenthal 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A. Dimitrios Colevas, MD principal investigator
Stanford University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ad/PNP and Fludarabine Phosphate in people with Recurrent Head and Neck Cancer, run by GeoVax, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. (time frame: up to 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03754933, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2025.