Trial Outcomes & Findings for Continuous 24h Intravenous Infusion of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in People With Primary Thoracic Malignancies or Carcinomas, Sarcomas or Germ Cell Neoplasms With Pleuropulmonary Metastases (NCT NCT02859415)
NCT ID: NCT02859415
Last Updated: 2022-04-05
Results Overview
MTD is defined as the number of participants experiencing a dose-limiting toxicity (DLT). A DLT is defined as Grade 4 or greater anemia or neutropenia exceeding 5 days duration, thrombocytopenia requiring transfusion, or Grade 3 or greater nonhematologic toxicity possibly, probably, or definitely related to the investigational therapy excluding alopecia during Cycle 1 of therapy.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
3 participants
Primary outcome timeframe
At the end of first 14 day cycle at each dose level
Results posted on
2022-04-05
Participant Flow
Study was terminated for slow/insufficient accrual before reaching phase II.
Participant milestones
| Measure |
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses..
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Overall Study
STARTED
|
1
|
2
|
|
Overall Study
COMPLETED
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses..
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Off treatment due to cardiac event
|
0
|
1
|
Baseline Characteristics
Continuous 24h Intravenous Infusion of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in People With Primary Thoracic Malignancies or Carcinomas, Sarcomas or Germ Cell Neoplasms With Pleuropulmonary Metastases
Baseline characteristics by cohort
| Measure |
Phase I Dose Level 1 Mithramycin 60 mcg/kg
n=1 Participants
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses..
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 Participants
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
Total
n=3 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 0 • n=93 Participants
|
49.35 years
STANDARD_DEVIATION 18.88 • n=4 Participants
|
52.33 years
STANDARD_DEVIATION 14.32 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=93 Participants
|
2 participants
n=4 Participants
|
3 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: At the end of first 14 day cycle at each dose levelMTD is defined as the number of participants experiencing a dose-limiting toxicity (DLT). A DLT is defined as Grade 4 or greater anemia or neutropenia exceeding 5 days duration, thrombocytopenia requiring transfusion, or Grade 3 or greater nonhematologic toxicity possibly, probably, or definitely related to the investigational therapy excluding alopecia during Cycle 1 of therapy.
Outcome measures
| Measure |
All Participants
n=3 Participants
All participants in phase I dose level 1 and dose level -1.
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
NA mcg/kg
The MTD was not found because we did not have enough participant participation.
|
—
|
PRIMARY outcome
Timeframe: every 8 weeks until at disease progression, approximately 3.5 monthsPopulation: One participant in the first group only received one dose, thus was not evaluable.
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
All Participants
All participants in phase I dose level 1 and dose level -1.
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 Participants
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Number of Participants Whose Best Response is a Complete Response (CR) or Partial Response (PR)
Complete Response
|
—
|
0 Participants
|
|
Number of Participants Whose Best Response is a Complete Response (CR) or Partial Response (PR)
Partial Response
|
—
|
0 Participants
|
SECONDARY outcome
Timeframe: baseline, Cycle 1 Day 4 (+/- 3 days), and possible treatment evaluation following Course 1Population: No data was collected thus this outcome measure was not done.
Studies on tumor tissue obtained during baseline /previous biopsy (if available), Cycle 1 Day 4(+/- 3 days), and possible treatment evaluation following Course 1. Plasma and blood will also be collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, Cycle 1 Day 4 (+/- 3 days), and possible treatment evaluation following Course 1Population: No data was collected thus this outcome measure was not done.
Studies on tumor tissue obtained during baseline /previous biopsy (if available), Cycle 1 Day 4(+/- 3 days), and possible treatment evaluation following Course 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, Cycle 1 Day 4 (+/- 3 days), and possible treatment evaluation following Course 1Population: No data was collected thus this outcome measure was not done.
Studies on tumor tissue obtained during baseline /previous biopsy (if available), Cycle 1 Day 4(+/- 3 days), and possible treatment evaluation following Course 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, Cycle 1 Day 4 (+/- 3 days), and possible treatment evaluation following Course 1Population: No data was collected thus this outcome measure was not done.
Studies on tumor tissue obtained during baseline /previous biopsy (if available), Cycle 1 Day 4(+/- 3 days), and possible treatment evaluation following Course 1.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, Cycle 1 Day 4 (+/- 3 days), and possible treatment evaluation following Course 1Population: No data was collected thus this outcome measure was not done.
Studies on tumor tissue obtained during baseline /previous biopsy (if available), Cycle 1 Day 4(+/- 3 days), and possible treatment evaluation following Course 1. Plasma and blood will also be collected.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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.
Outcome measures
| Measure |
All Participants
n=1 Participants
All participants in phase I dose level 1 and dose level -1.
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 Participants
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
|
1 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Cycle 1A DLT is defined as Grade 4 or greater anemia or neutropenia exceeding 5 days duration, thrombocytopenia requiring transfusion, or Grade 3 or greater nonhematologic toxicity possibly, probably, or definitely related to the investigational therapy excluding alopecia during Cycle 1 of therapy.
Outcome measures
| Measure |
All Participants
n=1 Participants
All participants in phase I dose level 1 and dose level -1.
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 Participants
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Number of Participants With a Dose-limiting Toxicity (DLT)
|
0 Participants
|
0 Participants
|
Adverse Events
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I Dose Level 1 Mithramycin 60 mcg/kg
n=1 participants at risk
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses..
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 participants at risk
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Investigations
Alanine aminotransferase
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 4 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 4 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
100.0%
2/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
100.0%
2/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
General disorders
Pain
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
Other adverse events
| Measure |
Phase I Dose Level 1 Mithramycin 60 mcg/kg
n=1 participants at risk
Phase I Dose Level 1 Mithramycin 60 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses..
|
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg
n=2 participants at risk
Phase I Dose Level -1 Mithramycin 60 mcg/kg followed by Mithramycin 30 mcg/kg
Mithramycin: Phase 1: 24 hour intravenous infusion of mithramycin given once every 14 days at escalating doses.
|
|---|---|---|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Investigations
Alanine aminotransferase increased
|
100.0%
1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 4 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
100.0%
2/2 • Number of events 19 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Investigations
Aspartate aminotransferase increased
|
100.0%
1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 3 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
100.0%
1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
100.0%
1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
100.0%
2/2 • Number of events 8 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Investigations
Lymphocyte count decreased
|
100.0%
1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
100.0%
2/2 • Number of events 3 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Gastrointestinal disorders
Nausea
|
100.0%
1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 2 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place