Head and Neck Cancer
Conditions
Keywords
Squamous cell carcinoma
Brief summary
This study has been designed to evaluate the safety and efficacy of giving seven injections of PepCan or placebo over approximately a 24-month period in subjects with head and neck cancers who achieved remission. PepCan may prove to be beneficial in treating many stages of HPV-related malignancies starting from infection to cancer. Safety, efficacy in terms of reduced cancer recurrence, immunological responses and profiles, and gut microbiome changes will be assessed.
Detailed description
This is a Phase I/II study to evaluate the efficacy and safety of an HPV therapeutic vaccine called PepCan (HPV-16 E6 peptides) in adults over a two (2) year period. Each subject will be receiving a total of 7 injections of PepCan (50 µg per peptide dose) or placebo (saline) at a 3:1 ratio in a randomized double-blinded design. Subjects will receive one injection every 3 weeks until they receive 4 injections. Then, subjects will receive one injection every 3 months until they receive a total of 7 injections. Subjects will have 2 more visits approximately 6 months apart after the last injection. Immunological assessment by enzyme-linked immunospot (ELISPOT) assay will be made at 4 time points (Visits 1, 5, 8, and 9), and by fluorescent activated cell sorter analysis will be made at times points at Visits 1, 3, 5, 6, 7, 8, and 9. Oral wash samples and stool samples will be collected at the Screening Visit, Visit 5, Visit 7 and Visit 8 for microbiome diversity analysis.
Interventions
BIOLOGICALPlacebo
0.9% Saline solution per dose administered intradermally in the extremities
BIOLOGICALPepCan
50 μg peptide + 0.3mL Candin® per dose administered intradermally in the extremities
Sponsors
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
PepCan or placebo randomized at a 3:1 ratio in a double-blinded design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Able to provide informed consent 2. Male or female 18 years of age or older 3. Squamous cell carcinoma of the head and neck who have completed curative therapy (surgery and/or radiation and/or chemotherapy) therapy within the previous 120 days 4. Performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 5. No Evidence of Disease (NED) based on clinical and/or radiographic evaluations 6. Vital Signs recorded 1. Blood pressure (≤160/95 mm Hg acceptable) 2. Heart rate (50-100 beats per min acceptable) 3. Respiratory rate (≥ 12 ≤25 breaths per min acceptable) 4. Temperature (≤100°F acceptable) 7. Blood work done at Screening Visit 1. White count (≥3x109/L acceptable) 2. Hemoglobin (≥ 7 g/dL acceptable) 8. Willing and able to comply with the requirements of the protocol
Exclusion criteria
1. Positive urine pregnancy test for women of childbearing potential 2. Being pregnant or attempting to be pregnant within the period of study participation 3. Women who are breast feeding or plan to breast feed within the period of study participation 4. Patients who are allergic to Candin® or yeast 5. History of severe asthma requiring emergency room visit or hospitalization within the past 5 years 6. Patients who have previously received PepCan 7. History of recurrence of squamous cell carcinoma of the head and neck 8. If in the opinion of the Principal Investigator or other Investigators, it is not in the best interest of the patient to enter or continue in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | 2 years | To evaluate the safety of a 7-injection regimen of PepCan, adverse events will be captured and assessed per NCI CTCAE Version 5.0 whether they are treatment-related or not by a physician. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Study completion, approximately 24 months after enrollment | To evaluate the efficacy, cancer recurrence rates will be compared between the PepCan and placebo arms. Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders. |
| Efficacy Analysis (Intention to Treat) - PepCan | Study completion, approximately 24 months after enrollment | Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders. The Intention-to-Treat outcome is based on the worst-case scenario and considers those who withdrew as non-responders. Patients who screen-failed or were considered ineligible were excluded from the ITT analysis. |
| Efficacy Analysis (Intention to Treat) - Placebo | Study completion, approximately 24 months after enrollment | Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders. The Intention-to-Treat outcome is based on the worst-case scenario and considers those who withdrew as non-responders. Patients who screen-failed or were considered ineligible were excluded from the ITT analysis. |
| Efficacy Analysis (Per Protocol) - PepCan | Study completion, approximately 24 months after enrollment | The Per Protocol outcome includes subjects who completed the study either by completing Visit 9 or having had recurrences. Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis. |
| Efficacy Analysis (Per Protocol) - Placebo | Study completion, approximately 24 months after enrollment | The Per Protocol outcome includes subjects who completed the study either by completing Visit 9 or having had recurrences. Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PepCan Four injections (one every 3 weeks) of PepCan, then three injections (one every 3 months) of PepCan for a total of 7 injections.
PepCan: 50 μg peptide + 0.3mL Candin® per dose administered intradermally in the extremities | 12 |
| Placebo Four injections (one every 3 weeks) of placebo, then three injections (one every 3 months) of placebo for a total of 7 injections.
Placebo: 0.9% Saline solution per dose administered intradermally in the extremities | 5 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | PepCan |
|---|---|---|---|
| Age, Continuous | 59.34 years STANDARD_DEVIATION 14 | 59.82 years STANDARD_DEVIATION 9.82 | 60.03 years STANDARD_DEVIATION 8.3 |
| Body mass index | 21.86 kg/m2 STANDARD_DEVIATION 4.41 | 22.17 kg/m2 STANDARD_DEVIATION 3.87 | 22.30 kg/m2 STANDARD_DEVIATION 3.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 16 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hematocrit | 32.96 % STANDARD_DEVIATION 4.64 | 35.55 % STANDARD_DEVIATION 5.56 | 36.63 % STANDARD_DEVIATION 5.73 |
| Hemoglobin | 10.88 g/dL STANDARD_DEVIATION 1.43 | 11.63 g/dL STANDARD_DEVIATION 1.81 | 11.94 g/dL STANDARD_DEVIATION 1.91 |
| Human Papillomavirus/P16 HPV/P16 negative | 1 Participants | 6 Participants | 5 Participants |
| Human Papillomavirus/P16 HPV/P16 positive | 3 Participants | 7 Participants | 4 Participants |
| Human Papillomavirus/P16 HPV/P16 unknown | 1 Participants | 4 Participants | 3 Participants |
| Human papillomavirus status Negative | 1 Participants | 1 Participants | 0 Participants |
| Human papillomavirus status Positive | 0 Participants | 0 Participants | 0 Participants |
| Human papillomavirus status Unknown | 4 Participants | 16 Participants | 12 Participants |
| P16 P16 negative | 0 Participants | 5 Participants | 5 Participants |
| P16 P16 positive | 3 Participants | 7 Participants | 4 Participants |
| P16 P16 unknown | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 7 Participants |
| Region of Enrollment United States | 5 participants | 17 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 15 Participants | 11 Participants |
| TNM Staging, Lymph node TNM Staging, Lymph node: N0 | 1 participants | 2 participants | 1 participants |
| TNM Staging, Lymph node TNM Staging, Lymph node: N1 | 2 participants | 3 participants | 1 participants |
| TNM Staging, Lymph node TNM Staging, Lymph node: N2 | 2 participants | 10 participants | 8 participants |
| TNM Staging, Lymph node TNM Staging, Lymph node: N3 | 0 participants | 2 participants | 2 participants |
| TNM Staging, Metastasis: M0 M0 | 5 participants | 17 participants | 12 participants |
| TNM Staging, Metastasis: M0 M1 | 0 participants | 0 participants | 0 participants |
| TNM Staging, Metastasis: M0 MX | 0 participants | 0 participants | 0 participants |
| TNM Staging, Tumor TNM Staging, Tumor: T1 | 0 Participants | 3 Participants | 3 Participants |
| TNM Staging, Tumor TNM Staging, Tumor: T2 | 4 Participants | 6 Participants | 2 Participants |
| TNM Staging, Tumor TNM Staging, Tumor: T3 | 1 Participants | 4 Participants | 3 Participants |
| TNM Staging, Tumor TNM Staging, Tumor: T4 | 0 Participants | 4 Participants | 4 Participants |
| Tumor location Site: Larynx | 0 Participants | 3 Participants | 3 Participants |
| Tumor location Site: Oral | 0 Participants | 3 Participants | 3 Participants |
| Tumor location Site: Pharynx | 5 Participants | 11 Participants | 6 Participants |
| White blood cells | 4.64 10^3 cells/μL STANDARD_DEVIATION 1.7 | 5.03 10^3 cells/μL STANDARD_DEVIATION 1.55 | 5.20 10^3 cells/μL STANDARD_DEVIATION 1.52 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 0 / 5 |
| other Total, other adverse events | 12 / 12 | 5 / 5 |
| serious Total, serious adverse events | 5 / 12 | 2 / 5 |
Outcome results
Primary
Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan.
To evaluate the safety of a 7-injection regimen of PepCan, adverse events will be captured and assessed per NCI CTCAE Version 5.0 whether they are treatment-related or not by a physician.
Time frame: 2 years
Population: Participants with side effects occurring with 5% or more injections.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | General Disorders and Site Administration Conditions: Injection site reaction | 23 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | General Disorders and Site Administration Conditions: Fatigue | 0 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Immune System Disorders : Allergic reaction | 2 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Injury, Poisoning and Procedural Complications : Vaccination complication | 4 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Metabolism and Nutrition Disorders: Hypokalemia | 1 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Nervous System Disorders : Dizziness | 1 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Nervous System Disorders : Headache | 2 adverse event |
| PepCan | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Skin and Subcutaneous Tissue Disorders : Pruritus | 1 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Skin and Subcutaneous Tissue Disorders : Pruritus | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | General Disorders and Site Administration Conditions: Injection site reaction | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Metabolism and Nutrition Disorders: Hypokalemia | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | General Disorders and Site Administration Conditions: Fatigue | 1 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Nervous System Disorders : Headache | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Immune System Disorders : Allergic reaction | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Nervous System Disorders : Dizziness | 0 adverse event |
| Placebo | Adverse Events - Evaluate Safety of a 7-injection Regimen of PepCan. | Injury, Poisoning and Procedural Complications : Vaccination complication | 1 adverse event |
Secondary
Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan
To evaluate the efficacy, cancer recurrence rates will be compared between the PepCan and placebo arms. Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders.
Time frame: Study completion, approximately 24 months after enrollment
Population: Patients who screen-failed or were considered ineligible were excluded from the ITT analysis and PP analysis..
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PepCan | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Non-recurrence | 5 Participants |
| PepCan | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Recurrence | 4 Participants |
| PepCan | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Withdrawn | 2 Participants |
| PepCan | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Ineligible | 1 Participants |
| Placebo | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Ineligible | 0 Participants |
| Placebo | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Non-recurrence | 4 Participants |
| Placebo | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Withdrawn | 0 Participants |
| Placebo | Cancer Recurrence Rate - Efficacy of a 7-injection Regimen of PepCan | Recurrence | 1 Participants |
Secondary
Efficacy Analysis (Intention to Treat) - PepCan
Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders. The Intention-to-Treat outcome is based on the worst-case scenario and considers those who withdrew as non-responders. Patients who screen-failed or were considered ineligible were excluded from the ITT analysis.
Time frame: Study completion, approximately 24 months after enrollment
Population: Patients who screen-failed or were considered ineligible were excluded from the ITT analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PepCan | Efficacy Analysis (Intention to Treat) - PepCan | Responder | 5 Participants |
| PepCan | Efficacy Analysis (Intention to Treat) - PepCan | Non-responder | 6 Participants |
| PepCan | Efficacy Analysis (Intention to Treat) - PepCan | Unknown | 1 Participants |
p-value: 0.3195% CI: [0.17, 0.77]Fisher Exact
Secondary
Efficacy Analysis (Intention to Treat) - Placebo
Patients with a non-recurrence status are defined as responders. Patients with a recurrence status are defined as non-responders. The Intention-to-Treat outcome is based on the worst-case scenario and considers those who withdrew as non-responders. Patients who screen-failed or were considered ineligible were excluded from the ITT analysis.
Time frame: Study completion, approximately 24 months after enrollment
Population: Patients who screen-failed or were considered ineligible were excluded from the ITT analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PepCan | Efficacy Analysis (Intention to Treat) - Placebo | Responder | 4 Participants |
| PepCan | Efficacy Analysis (Intention to Treat) - Placebo | Non-responder | 1 Participants |
| PepCan | Efficacy Analysis (Intention to Treat) - Placebo | Unknown | 0 Participants |
p-value: 0.3195% CI: [0.28, 0.99]Fisher Exact
Secondary
Efficacy Analysis (Per Protocol) - PepCan
The Per Protocol outcome includes subjects who completed the study either by completing Visit 9 or having had recurrences. Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis.
Time frame: Study completion, approximately 24 months after enrollment
Population: Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PepCan | Efficacy Analysis (Per Protocol) - PepCan | Responder | 5 Participants |
| PepCan | Efficacy Analysis (Per Protocol) - PepCan | Non-responder | 4 Participants |
| PepCan | Efficacy Analysis (Per Protocol) - PepCan | Unknown | 3 Participants |
p-value: 0.5895% CI: [0.21, 0.86]Fisher Exact
Secondary
Efficacy Analysis (Per Protocol) - Placebo
The Per Protocol outcome includes subjects who completed the study either by completing Visit 9 or having had recurrences. Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis.
Time frame: Study completion, approximately 24 months after enrollment
Population: Patients who screen-failed, withdrew, or were considered ineligible (after randomization) are excluded from the PP analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PepCan | Efficacy Analysis (Per Protocol) - Placebo | Responder | 4 Participants |
| PepCan | Efficacy Analysis (Per Protocol) - Placebo | Non-responder | 1 Participants |
| PepCan | Efficacy Analysis (Per Protocol) - Placebo | Unknown | 0 Participants |
p-value: 0.5895% CI: [0.28, 0.99]Fisher Exact