Trial Outcomes & Findings for Safety and Efficacy of Repeat Administration of Ad/PNP and Fludarabine Phosphate in Patients With Local Head/Neck Cancer (NCT NCT03754933)

Last Updated: 2025-03-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

up to 7 months

Results posted on

2025-03-27

Participant Flow

10 subjects provided consent; however, only 8 subjects were assigned to the treatment group as one subject died and one subject was determined ineligible (per protocol entry criteria) prior to treatment assignment.

Participant milestones

Participant milestones
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=20 lesions Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Age, Continuous	58.8 years STANDARD_DEVIATION 8.01 • n=39 Participants
Sex: Female, Male Female	2 Participants n=39 Participants
Sex: Female, Male Male	6 Participants n=39 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=39 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants
Race (NIH/OMB) Asian	5 Participants n=39 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants
Race (NIH/OMB) Black or African American	0 Participants n=39 Participants
Race (NIH/OMB) White	3 Participants n=39 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants
Disease History - Duration of Time from Initial Diagnosis (months)	44.90 months STANDARD_DEVIATION 18.184 • n=39 Participants
Disease History - Staging at First Diagnosis II	1 Participants n=39 Participants
Disease History - Staging at First Diagnosis III	3 Participants n=39 Participants
Disease History - Staging at First Diagnosis IV	3 Participants n=39 Participants
Disease History - Staging at First Diagnosis Missing	1 Participants n=39 Participants
Disease History - Histological Type Squamous cell carcinoma	6 Participants n=39 Participants
Disease History - Histological Type Other	2 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Progression - Local	1 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Recurrence - Local	4 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Regional	1 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Progression - Regional	3 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Recurrence - Regional	2 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Specification Metastasis	5 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Hypopharynx	1 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Larynx	1 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Lymph node	4 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Nasal cavity	1 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Other	4 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Pharynx	2 Participants n=39 Participants
Disease History - Progression/Recurrence/Metastasis Location Soft tissue	1 Participants n=39 Participants
Disease Characteristics at Baseline - Summary of Diameters of Target Lesions	92.93 mm STANDARD_DEVIATION 76.255 • n=20 lesions
Disease Characteristics at Baseline - Summary of Diameters of For-Injection Lesions	50.30 mm STANDARD_DEVIATION 36.542 • n=20 lesions
Disease Characteristics at Baseline - ECOG Grade 0	1 Participants n=39 Participants
Disease Characteristics at Baseline - ECOG Grade 1	5 Participants n=39 Participants
Disease Characteristics at Baseline - ECOG Grade 2	2 Participants n=39 Participants

PRIMARY outcome

Timeframe: up to 7 months

Population: Defined as all participants who received any intratumoral administrations of Ad/PNP or any infusion of F-araAMP.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Serious Adverse Events	5 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Fatal SAEs	0 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE	8 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE Related to Study Treatment	8 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE Related to Non-Study Treatment	1 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE Grade 3 or Greater	7 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Dose Limiting Toxicity TEAE	0 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE Leading to Study Discontinuation	1 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any TEAE Grade 3 or Greater Related to Study Treatment	3 Participants
Safety Measures (Adverse Events and Laboratory Parameters) With Repeat Cycles of Treatment. Any Serious TEAE	5 Participants

SECONDARY outcome

Timeframe: up to 7 months

Population: All participants who received at least three intratumoral administrations of Ad/PNP and any infusion of F-araAMP.

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.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1. Stable Disease	3 Participants
Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1. Progressive Disease	2 Participants
Best Overall Response for Injected Tumors During 5 Cycles of Treatment as Determined by RECIST 1.1. Not Evaluable	3 Participants

SECONDARY outcome

Timeframe: up to 7 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.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Progression Free Survival (PFS) - Time From First Intratumoral Injection to Date of Progression or Death, Calculated in Months	7.0 Months Interval 0.39 to Not enough participants achieved response to calculate upper 95% CI

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Probability of No Progressive Disease or Death and 95% CI Up to 6 Months (%)	56.3 percentage of subjects Interval 14.7 to 84.2

SECONDARY outcome

Timeframe: up to 7 months

Population: All participants who received at least three intratumoral administrations of Ad/PNP and any infusion of F-araAMP.

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.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Overall Survival (OS) - Time From First Intratumoral Injection to Date of Death up to 60 Days Post Last Injection	7.0 Months Interval 0.69 to Not enough participants achieved response to calculate upper 95% CI

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 Participants Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.
Probability of No Death and 95% CI up to 1 Month and up to 6 Months Up to 1 month	87.5 percentage of subjects Interval 38.7 to 98.1
Probability of No Death and 95% CI up to 1 Month and up to 6 Months Up to 6 months	72.9 percentage of subjects Interval 27.6 to 92.5

Adverse Events

Ad/PNP + Fludarabine Phosphate, 5 Cycles

Serious events: 5 serious events

Other events: 8 other events

Deaths: 3 deaths

Participants Who Were Enrolled But Not Randomized

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Ad/PNP + Fludarabine Phosphate, 5 Cycles n=8 participants at risk Ad/PNP: Ad/PNP is a replication defective adenoviral vector expressing E. coli Purine Nucleoside Phosphorylase Fludarabine Phosphate: Fludarabine phosphate is an anticancer agent currently used for treatment of patients with chronic lymphocytic leukemia.	Participants Who Were Enrolled But Not Randomized Participants who were enrolled but not randomized
Infections and infestations Pneumonia	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
General disorders Fever	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
Gastrointestinal disorders Vomiting	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
Cardiac disorders Supraventricular tachycardia	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
Gastrointestinal disorders Dysphagia	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.
Metabolism and nutrition disorders Dehydration	12.5% 1/8 • Number of events 1 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.	— 0/0 • All-cause mortality was assessed from signing of informed consent up to 6 months. Serious and Other Adverse Events were assessed from initiation of study treatment (Day 1) up to 6 months. All adverse events regardless of seriousness or relationship to study drug were recorded. Only All-Cause Mortality was assessed in the 2 participants that were enrolled but not randomized. All-Cause mortality, SAEs and Other Adverse Events were assessed in the safety population, which was defined as all participants who received any intratumoral administrations of Ad/PNP or an infusion of F-araAMP.

Other adverse events

Additional Information

Kelly T. McKee, Jr., MD, MPH

GeoVax, Inc.

Phone: (678) 384-7220

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI agrees that a MULTI CENTER PUBLICATION (MCP) coordinated by SPONSOR will be the first publication to present the pooled STUDY results. PI agrees not to independently publish, present or otherwise disclose any results of the STUDY until a MCP is published. Following the MCP, or if the MCP is not submitted for publication within18 months of database lock or any earlier termination of the STUDY, PI shall have the right to publish or present materials related to the STUDY.
Publication restrictions are in place

Restriction type: OTHER