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AMP-224, a PD-1 Inhibitor, With Stereotactic Body Radiation Therapy in Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT02298946
Recruitment Status : Completed
First Posted : November 24, 2014
Results First Posted : February 22, 2019
Last Update Posted : February 22, 2019
Sponsor:
Information provided by (Responsible Party):
Tim Greten, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Colorectal Cancer
Colorectal Neoplasms
Colorectal Carcinoma
Interventions Drug: AMP-224
Radiation: Stereotactic Body Radiation Therapy(SBRT)
Drug: Cyclophosphamide
Enrollment 17
Recruitment Details  
Pre-assignment Details  
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Period Title: Overall Study
Started 8 9
Completed 4 8
Not Completed 4 1
Reason Not Completed
Did not receive treatment             2             0
Unevaluable             2             1
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224 Total
Hide Arm/Group Description

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Total of all reporting groups
Overall Number of Baseline Participants 8 9 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
  37.5%
5
  55.6%
8
  47.1%
>=65 years
5
  62.5%
4
  44.4%
9
  52.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 9 participants 17 participants
60.4  (17.2) 57.3  (14.5) 58.8  (15.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
Female
3
  37.5%
3
  33.3%
6
  35.3%
Male
5
  62.5%
6
  66.7%
11
  64.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  12.5%
0
   0.0%
1
   5.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  12.5%
2
  22.2%
3
  17.6%
White
6
  75.0%
7
  77.8%
13
  76.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
Not meeting the definition for Hispanic or Latino
7
  87.5%
9
 100.0%
16
  94.1%
Mexican,Puerto Rican,Cuban,Central or So. Amer/Oth
1
  12.5%
0
   0.0%
1
   5.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 8 participants 9 participants 17 participants
8 9 17
Count of Participants with Pre-Treatment Biopsies  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
7
  87.5%
9
 100.0%
16
  94.1%
1.Primary Outcome
Title Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 24 months and 8 days
Hide Outcome Measure Data
Hide Analysis Population Description
One patient (on dose level 1) after signing consent while waiting for radiation dosing, developed a spinal cord compression that needed emergent care at the local hospital. This patient was not treated. One patient (on dose level 1) after signing consent, developed a bowel obstruction prior to treatment.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
6
 100.0%
9
 100.0%
2.Secondary Outcome
Title Duration of Response in Patients With Colorectal Cancer During and Following Treatment With AMP-224 in Combination With SBRT
Hide Description Duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is recorded first) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is complete 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 is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame 12 months
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Hide Analysis Population Description
Zero participants were analyzed because no participants experienced a CR or PR.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Number of Participants in Which Specimens Were Collected for Pre and Post Pharmacokinetic (PK) AMP-224 Analyses
Hide Description This outcome measure only represents the number of participants with metastatic colorectal cancer who had specimens collected for pre and post pharmacokinetic (PK) AMP-224 analyses.
Time Frame Baseline and post infusion AMP-224 (e.g. 15 minutes after infusion ended)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 6 9
Measure Type: Count of Participants
Unit of Measure: Participants
Pre AMP-224
6
 100.0%
9
 100.0%
Post AMP-224
6
 100.0%
9
 100.0%
4.Secondary Outcome
Title Overall Survival in Patients With Colorectal Cancer Following Treatment With AMP-224 in Combination With SBRT
Hide Description Overall survival is defined as the time from treatment start date until date of death or date last known alive.
Time Frame Baseline to end of study, which is date of death. Average time participants were followed was 10.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients were follow up post completion of the treatment medications for survival until date of their death. 2 patients were not evaluable since they did not receive treatment. 1 patient was lost to follow up after 3 cycles of treatment due to brain metastasis and treatment in another state.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 6 9
Median (95% Confidence Interval)
Unit of Measure: months
4.3
(1.2 to 8.9)
9.0
(1.5 to 21.3)
5.Secondary Outcome
Title Count of Participants With Post-Treatment Biopsies
Hide Description Mandatory post treatment biopsies of the tumor were attempted on all patients.
Time Frame Post treatment, day 29 +/- 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 8 9
Measure Type: Count of Participants
Unit of Measure: Participants
6
  75.0%
0
   0.0%
6.Secondary Outcome
Title Median Progression-free Survival in Patients With Colorectal Cancer
Hide Description Progression free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is at least a 20% increase in the sum of the 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 5mm. (Note: the appearance of one or more new lesions is also considered progressions).
Time Frame Baseline to disease progression, an average of 2.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 6 9
Median (95% Confidence Interval)
Unit of Measure: months
1.7
(0.9 to 3.3)
2.7
(0.3 to 12.8)
7.Secondary Outcome
Title Objective Response Rate
Hide Description Objective response will be evaluated according to the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and is defined as Complete Response + Partial Response. Briefly, complete response (CR) is defined as the disappearance of all target lesions, and Partial Response is defined as "at least" 30% decrease in the sum of the diameters of the target lesions from baseline measurement.
Time Frame Restaging was done every 8 weeks for an average of 2.6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All patients had restaging evaluations completed as per protocol. Response criteria in solid tumors(RECIST) were completed on every trial participate. No partial or complete responses were found in any patients.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 6 9
Measure Type: Number
Unit of Measure: percentage of participants
0 0
8.Secondary Outcome
Title Immunogenicity of AMP-224 as Measured by Human Anti-Murine Antibodies (HAMA) and Human Anti-Chimeric Antibodies (HACA) Concentrations
Hide Description Blood samples were collected to measure HAMA and HACA concentrations using the ELISA method in all patients.
Time Frame Baseline, D1, D29, and D57 (pre-infusion), D79, D85 and 90 days post last dose (D169)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected and not analyzed because the outside laboratory declined to run specimens with a negative clinical trial.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Terminal Elimination Half-Life of AMP-224
Hide Description Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time Frame 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected and not analyzed because the outside laboratory declined to run specimens with a negative clinical trial.
Arm/Group Title All Participants
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0 Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Area of the Curve (AUC) of AMP-224
Hide Description The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. The lower limit of quantification (LLOQ) is the smallest concentration of the drug that can be reliably measured.
Time Frame Pre and post-infusion with all the AMP infusion and Day 1 at 8, 15, 29, 43, 57, and 71 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected and not analyzed because the outside laboratory declined to run specimens with a negative clinical trial.
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Time to Maximum Observed Plasma Concentration (Tmax) of AMP-224
Hide Description Time maximum drug absorption is reached in the blood following administration of AMP-224.
Time Frame 12.7 hours following intravenous (IV) infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
Data was collected and not analyzed because the outside laboratory declined to run specimens with a negative clinical trial.
Arm/Group Title All Participants
Hide Arm/Group Description:

Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0 Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days

AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses.

Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days

Cyclophosphamide: 200mg/m(2) IV on day 0

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Date treatment consent signed to date off study, approximately 24 months and 8 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Hide Arm/Group Description Dose Level 1 (DL1) Cyclophosphamide (CTX) 200mg/m(2) intravenous (IV) on day 0, stereotactic body radiation therapy (SBRT) 8 (gray)Gy x 1 day on day 0, AMP-224 10mg/kg on day 1 then every (q)14 days AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses. Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days Cyclophosphamide: 200mg/m(2) IV on day 0 Dose Level 2 (DL2) CTX 200mg/m(2) IV on day 0, SBRT 8Gy x 3 day on days -2, -1, 0, AMP-224 10mg/kg on day 1 then q14 days AMP-224: 10mg/kg on day 1 then every 14 days for a total of 6 doses. Stereotactic Body Radiation Therapy(SBRT): Dose Level 1: 8Gy x 1 day Dose Level 2: 8Gy x 3 days Cyclophosphamide: 200mg/m(2) IV on day 0
All-Cause Mortality
DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)      9/9 (100.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/6 (66.67%)      2/9 (22.22%)    
General disorders     
Death NOS  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Hyperuricemia  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify  1 [1]  3/6 (50.00%)  3 0/9 (0.00%)  0
Nervous system disorders     
Headache  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Psychiatric disorders     
Confusion  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  0/6 (0.00%)  0 1/9 (11.11%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
malignant neoplasm
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
DL1 - CTX, SBRTx1 Day, & AMP-224 DL2 - CTX, SBRTx3 Days, and AMP-224
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      9/9 (100.00%)    
Blood and lymphatic system disorders     
Anemia  1  5/6 (83.33%)  12 8/9 (88.89%)  16
Cardiac disorders     
Chest pain - cardiac  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Endocrine disorders     
Blurred vision  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Hypothyroidism  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Gastrointestinal disorders     
Constipation  1  2/6 (33.33%)  2 2/9 (22.22%)  3
Diarrhea  1  2/6 (33.33%)  2 3/9 (33.33%)  3
Nausea  1  3/6 (50.00%)  4 4/9 (44.44%)  9
Vomiting  1  3/6 (50.00%)  4 2/9 (22.22%)  2
General disorders     
Chills  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Edema limbs  1  0/6 (0.00%)  0 1/9 (11.11%)  2
Fatigue  1  4/6 (66.67%)  8 5/9 (55.56%)  6
Fever  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Infusion related reaction  1  3/6 (50.00%)  7 5/9 (55.56%)  12
Pain  1  4/6 (66.67%)  9 5/9 (55.56%)  10
Infections and infestations     
Sinusitis  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Urinary tract infection  1  0/6 (0.00%)  0 2/9 (22.22%)  2
Investigations     
Activated partial thromboplastin time prolonged  1  5/6 (83.33%)  14 8/9 (88.89%)  19
Alanine aminotransferase increased  1  4/6 (66.67%)  6 3/9 (33.33%)  3
Alkaline phosphatase increased  1  4/6 (66.67%)  8 5/9 (55.56%)  8
Aspartate aminotransferase increased  1  4/6 (66.67%)  5 4/9 (44.44%)  7
Blood bilirubin increased  1  3/6 (50.00%)  4 1/9 (11.11%)  1
Cholesterol high  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Creatinine increased  1  1/6 (16.67%)  1 1/9 (11.11%)  3
Lymphocyte count decreased  1  3/6 (50.00%)  8 8/9 (88.89%)  30
Lymphocyte count increased  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Pancreatic enzymes decreased  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Platelet count decreased  1  1/6 (16.67%)  3 1/9 (11.11%)  1
Serum amylase increased  1  1/6 (16.67%)  1 2/9 (22.22%)  4
Weight loss  1  0/6 (0.00%)  0 1/9 (11.11%)  1
White blood cell decreased  1  1/6 (16.67%)  1 2/9 (22.22%)  4
Metabolism and nutrition disorders     
Anorexia  1  3/6 (50.00%)  3 2/9 (22.22%)  2
Dehydration  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Hyperkalemia  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Hyperuricemia  1  0/6 (0.00%)  0 2/9 (22.22%)  2
Hypoalbuminemia  1  4/6 (66.67%)  6 5/9 (55.56%)  7
Hypokalemia  1  1/6 (16.67%)  1 2/9 (22.22%)  2
Hypomagnesemia  1  2/6 (33.33%)  2 0/9 (0.00%)  0
Hyponatremia  1  3/6 (50.00%)  5 4/9 (44.44%)  6
Hypophosphatemia  1  1/6 (16.67%)  1 4/9 (44.44%)  8
Musculoskeletal and connective tissue disorders     
Generalized muscle weakness  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Neck pain  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Nervous system disorders     
Cognitive disturbance  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Dizziness  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Headache  1  2/6 (33.33%)  2 1/9 (11.11%)  3
Presyncope  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Somnolence  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Psychiatric disorders     
Anxiety  1  1/6 (16.67%)  1 1/9 (11.11%)  3
Confusion  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Insomnia  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Renal and urinary disorders     
Renal and urinary disorders - Other, specify  1 [1]  0/6 (0.00%)  0 1/9 (11.11%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/6 (16.67%)  1 1/9 (11.11%)  1
Dyspnea  1  1/6 (16.67%)  1 3/9 (33.33%)  4
Hypoxia  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Pleural effusion  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders - Other, specify  1 [2]  1/6 (16.67%)  1 0/9 (0.00%)  0
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  1/6 (16.67%)  1 0/9 (0.00%)  0
Papulopustular rash  1  0/6 (0.00%)  0 1/9 (11.11%)  1
Pruritus  1  0/6 (0.00%)  0 2/9 (22.22%)  2
Skin and subcutaneous tissue disorders - Other, specify  1 [3]  0/6 (0.00%)  0 1/9 (11.11%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
urinary discomfort
[2]
outside CT scan, suggests pt might have pneumonia or increased lung lesion
[3]
diaphoresis
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Tim F. Greten
Organization: National Cancer Institute
Phone: 301-451-4723
EMail: gretentf@mail.nih.gov
Layout table for additonal information
Responsible Party: Tim Greten, M.D., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02298946     History of Changes
Other Study ID Numbers: 150021
15-C-0021
First Submitted: November 21, 2014
First Posted: November 24, 2014
Results First Submitted: October 4, 2018
Results First Posted: February 22, 2019
Last Update Posted: February 22, 2019