Ignite Creation Date:
2024-05-06 @ 12:26 PM
Last Modification Date:
2024-10-26 @ 12:58 PM
Study NCT ID:
NCT03754933
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-08-31
First Post:
2018-10-19
Brief Title:
Safety and Efficacy of Repeat Administration of AdPNP and Fludarabine Phosphate in Patients With Local HeadNeck Cancer
Sponsor:
GeoVax Inc
Organization:
GeoVax Inc
Study Overview
Official Title:
Phase 12 Open-label Study Evaluating Safety of Repeat Administration of AdPNP-F-araAMP AdPNP Administered Intratumorally Followed by Intravenous Fludarabine Phosphate in Subjects With Recurrent Local Head and Neck Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary Objective The primary objective of the study is to evaluate the safety of repeat administration of a dose level of AdPNP 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 AdPNP plus F-araAMP
FDA Office of Orphan Drugs Division is a source of funding for the overall project
Secondary Objective The secondary objective is to evaluate the antitumor activity of repeat administration of AdPNP plus F-araAMP
FDA Office of Orphan Drugs Division is a source of funding for the overall project
Detailed Description:
1 Mechanism of action The study drug AdPNP-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 ie 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 25 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
2 Tumor response with AdPNP-F-araAMP in Phase 1 Study The safety and efficacy of AdPNP-F-araAMP has been evaluated in a Phase 1 study PNP-001 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 AdPNP over 2 days and IV F-araAMP phosphate over 3 days The overall response rate CRPR 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 AdPNP 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 AdPNP seen in the Phase 1 study supports further clinical evaluation of repeat administration of AdPNP IT and F-araAMP phosphate infusion for patients with HNSCC
3 Purpose of the Study Based upon the tumor response seen with a single administration of the two highest dose levels of AdPNP-F-araAMP in the Phase 1 study PNP plans to investigate the safety and assess anti-tumor activity of repeat cycles of injection of AdPNP F-araAMP in patients with advanced head and neck cancer Subjects in the study will have RECIST 11 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 12 trial are intended to support the safety of repeat dosing in further clinical investigation
4 Study Design The trial is designed as a single-arm study to evaluate the safety of repeat cycles of AdPNP and F-araAMP in patients with recurrent HNSCC with tumors accessible for injection AdPNP 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 AdPNP-F-araAMP every 4 weeks ie 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 tumors will be assessed by physical examination as well as by radiographic imaging All subjects will be monitored for adverse events during study participation
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 ie 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 25 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
2 Tumor response with AdPNP-F-araAMP in Phase 1 Study The safety and efficacy of AdPNP-F-araAMP has been evaluated in a Phase 1 study PNP-001 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 AdPNP over 2 days and IV F-araAMP phosphate over 3 days The overall response rate CRPR 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 AdPNP 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 AdPNP seen in the Phase 1 study supports further clinical evaluation of repeat administration of AdPNP IT and F-araAMP phosphate infusion for patients with HNSCC
3 Purpose of the Study Based upon the tumor response seen with a single administration of the two highest dose levels of AdPNP-F-araAMP in the Phase 1 study PNP plans to investigate the safety and assess anti-tumor activity of repeat cycles of injection of AdPNP F-araAMP in patients with advanced head and neck cancer Subjects in the study will have RECIST 11 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 12 trial are intended to support the safety of repeat dosing in further clinical investigation
4 Study Design The trial is designed as a single-arm study to evaluate the safety of repeat cycles of AdPNP and F-araAMP in patients with recurrent HNSCC with tumors accessible for injection AdPNP 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 AdPNP-F-araAMP every 4 weeks ie 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 tumors will be assessed by physical examination as well as by radiographic imaging All subjects will be monitored for adverse events during study participation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 14271 | REGISTRY | IND | httpsreporternihgovquickSearchR01FD005746-01A1 |
| R01FD005746-01A1 | FDA | None | None |