Trial Outcomes & Findings for Safety Study of Adenovirus/PNP Coupled With Fludarabine Phosphate to Treat Solid Tumors (NCT NCT01310179)
NCT ID: NCT01310179
Last Updated: 2015-06-10
Results Overview
Number of participants who had the most frequently observed undesirable effects after exposure to study drug
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
Entry through Study Day 56
Results posted on
2015-06-10
Participant Flow
Participant milestones
| Measure |
Ad/PNP and Fludarabine Monophosphate
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety Study of Adenovirus/PNP Coupled With Fludarabine Phosphate to Treat Solid Tumors
Baseline characteristics by cohort
| Measure |
Ad/PNP and Fludarabine Monophosphate
n=12 Participants
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Karnofsky Performance Status Score
100%
|
2 participants
n=5 Participants
|
|
Karnofsky Performance Status Score
90%
|
3 participants
n=5 Participants
|
|
Karnofsky Performance Status Score
80%
|
3 participants
n=5 Participants
|
|
Karnofsky Performance Status Score
70%
|
4 participants
n=5 Participants
|
|
Tumor Site
Neck
|
6 participants
n=5 Participants
|
|
Tumor Site
Cheek
|
1 participants
n=5 Participants
|
|
Tumor Site
Hard Palate
|
1 participants
n=5 Participants
|
|
Tumor Site
Tonsil
|
1 participants
n=5 Participants
|
|
Tumor Site
Lower Lip
|
1 participants
n=5 Participants
|
|
Tumor Site
Scalp
|
1 participants
n=5 Participants
|
|
Tumor Site
Lower Extremities
|
1 participants
n=5 Participants
|
|
Tumor Histology
squamous cell carcinoma
|
8 participants
n=5 Participants
|
|
Tumor Histology
adenoid cycstic carcinoma
|
2 participants
n=5 Participants
|
|
Tumor Histology
melanoma
|
2 participants
n=5 Participants
|
|
Recurrence
Local
|
7 participants
n=5 Participants
|
|
Recurrence
Regional
|
4 participants
n=5 Participants
|
|
Recurrence
Distant
|
1 participants
n=5 Participants
|
|
Non-Target Lesions
Present
|
7 participants
n=5 Participants
|
|
Non-Target Lesions
Not Present
|
5 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Entry through Study Day 56Number of participants who had the most frequently observed undesirable effects after exposure to study drug
Outcome measures
| Measure |
Ad/PNP and Fludarabine Monophosphate
n=12 Participants
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first three cohorts will receive 3x10e11 VP for 3 injections and 5, 15 or 25 mg/m2 of F-araAMP daily for 3 days. Subject in the fourth cohort will receive 3x10e12 VP for 3 injections and the highest tolerated dose of F-araAMP daily for 3 days.
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
Number of Participants With Side Effects After Ad/PNP-F-araAMP Treatment
nausea
|
5 participants
|
|
Number of Participants With Side Effects After Ad/PNP-F-araAMP Treatment
injection site symptoms
|
12 participants
|
|
Number of Participants With Side Effects After Ad/PNP-F-araAMP Treatment
fatigue
|
8 participants
|
|
Number of Participants With Side Effects After Ad/PNP-F-araAMP Treatment
facial pain
|
8 participants
|
SECONDARY outcome
Timeframe: Entry through Study Day 56Measurement of tumor response to study drug, as measured by the percentage of change in tumor volume as measured by a physicial measurement using a ruler
Outcome measures
| Measure |
Ad/PNP and Fludarabine Monophosphate
n=12 Participants
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first three cohorts will receive 3x10e11 VP for 3 injections and 5, 15 or 25 mg/m2 of F-araAMP daily for 3 days. Subject in the fourth cohort will receive 3x10e12 VP for 3 injections and the highest tolerated dose of F-araAMP daily for 3 days.
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
Treatment Outcome and Percent Change in Tumor Volume
Stable (+20% to -30%)
|
5 participants
|
|
Treatment Outcome and Percent Change in Tumor Volume
Partial Response (>-30%)
|
5 participants
|
|
Treatment Outcome and Percent Change in Tumor Volume
Progression (>+20%)
|
2 participants
|
Adverse Events
Ad/PNP and Fludarabine Monophosphate
Serious events: 8 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ad/PNP and Fludarabine Monophosphate
n=12 participants at risk
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days..
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
Metabolism and nutrition disorders
dehydration
|
8.3%
1/12 • 56 days
|
|
Cardiac disorders
pericardial effusion
|
8.3%
1/12 • 56 days
|
|
Cardiac disorders
cardiac tamponade
|
8.3%
1/12 • 56 days
|
|
General disorders
pain
|
8.3%
1/12 • 56 days
|
|
Gastrointestinal disorders
nausea/vomiting
|
8.3%
1/12 • 56 days
|
|
Infections and infestations
bacteremia
|
8.3%
1/12 • 56 days
|
|
Nervous system disorders
partial seizure
|
8.3%
1/12 • 56 days
|
|
Musculoskeletal and connective tissue disorders
lower extremity weakness
|
8.3%
1/12 • 56 days
|
|
Infections and infestations
chronic wound infection
|
8.3%
1/12 • 56 days
|
Other adverse events
| Measure |
Ad/PNP and Fludarabine Monophosphate
n=12 participants at risk
Ad/PNP will be injected three times into the tumor over 2 days followed by three daily intravenous infusions of F-araAMP (fludarabine monophosphate). Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days..
Ad/PNP and fludarabine monophosphate: Subjects in the first 3 cohorts will receive 3x10e11 VP for 3 injections and escalating dose levels of F-araAMP (15, 45, and 75 mg/m2 in each sequential cohort) daily for 3 days. The fourth cohort will receive 3x10e12 for 3 injections and 75 mg/m2 fludarabine daily for 3 days.
|
|---|---|
|
General disorders
injection site symptoms
|
100.0%
12/12 • 56 days
|
|
General disorders
fatigue
|
66.7%
8/12 • 56 days
|
|
General disorders
facial pain
|
66.7%
8/12 • 56 days
|
|
Gastrointestinal disorders
nausea
|
41.7%
5/12 • 56 days
|
|
General disorders
flu-like symptoms
|
33.3%
4/12 • 56 days
|
|
Nervous system disorders
dizziness
|
33.3%
4/12 • 56 days
|
|
Nervous system disorders
headache
|
33.3%
4/12 • 56 days
|
|
Metabolism and nutrition disorders
decreased lymphocytes
|
33.3%
4/12 • 56 days
|
|
Metabolism and nutrition disorders
decreased hemoglobin
|
33.3%
4/12 • 56 days
|
|
Metabolism and nutrition disorders
decreased/loss of appetite
|
33.3%
4/12 • 56 days
|
|
Nervous system disorders
paresthesia
|
33.3%
4/12 • 56 days
|
|
General disorders
non-cardiac chest pain
|
25.0%
3/12 • 56 days
|
|
General disorders
facial edema
|
25.0%
3/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
25.0%
3/12 • 56 days
|
|
Vascular disorders
hypertension
|
25.0%
3/12 • 56 days
|
|
Infections and infestations
yeast infection
|
25.0%
3/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
sore throat
|
25.0%
3/12 • 56 days
|
|
Musculoskeletal and connective tissue disorders
back pain
|
16.7%
2/12 • 56 days
|
|
General disorders
lower extremity edema
|
16.7%
2/12 • 56 days
|
|
Skin and subcutaneous tissue disorders
rash
|
16.7%
2/12 • 56 days
|
|
Skin and subcutaneous tissue disorders
pruritis
|
16.7%
2/12 • 56 days
|
|
Musculoskeletal and connective tissue disorders
neck stiffness
|
16.7%
2/12 • 56 days
|
|
Gastrointestinal disorders
dysphagia
|
16.7%
2/12 • 56 days
|
|
Cardiac disorders
tachycardia
|
16.7%
2/12 • 56 days
|
|
Vascular disorders
hypotension
|
16.7%
2/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
16.7%
2/12 • 56 days
|
|
Gastrointestinal disorders
constipation
|
16.7%
2/12 • 56 days
|
|
Nervous system disorders
syncope
|
16.7%
2/12 • 56 days
|
|
Musculoskeletal and connective tissue disorders
arm pain
|
8.3%
1/12 • 56 days
|
|
Gastrointestinal disorders
vomiting
|
8.3%
1/12 • 56 days
|
|
Gastrointestinal disorders
diarrhea
|
8.3%
1/12 • 56 days
|
|
Metabolism and nutrition disorders
increased AST
|
8.3%
1/12 • 56 days
|
|
General disorders
fever
|
8.3%
1/12 • 56 days
|
|
Renal and urinary disorders
urinary urgency
|
8.3%
1/12 • 56 days
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
8.3%
1/12 • 56 days
|
|
General disorders
chills
|
8.3%
1/12 • 56 days
|
|
Endocrine disorders
hypothyroidism
|
8.3%
1/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
atelectasis
|
8.3%
1/12 • 56 days
|
|
Cardiac disorders
pericardial effusion
|
8.3%
1/12 • 56 days
|
|
Infections and infestations
upper respiratory infection
|
8.3%
1/12 • 56 days
|
|
General disorders
localized edema
|
8.3%
1/12 • 56 days
|
|
Skin and subcutaneous tissue disorders
periorbital edema
|
8.3%
1/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
bronchospasm
|
8.3%
1/12 • 56 days
|
|
Infections and infestations
wound infection
|
8.3%
1/12 • 56 days
|
|
Metabolism and nutrition disorders
dehydration
|
8.3%
1/12 • 56 days
|
|
Respiratory, thoracic and mediastinal disorders
wheezing
|
8.3%
1/12 • 56 days
|
|
Renal and urinary disorders
acute renal failure
|
8.3%
1/12 • 56 days
|
|
Gastrointestinal disorders
oral mucositis
|
8.3%
1/12 • 56 days
|
|
Investigations
weight loss
|
8.3%
1/12 • 56 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place