Trial Outcomes & Findings for 0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma (NCT NCT00729807)

Last Updated: 2019-08-16

Results Overview

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum of the longest diameter since the treatment started. (Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, J., Van Glabbeke, M., van Oosterom, A.T., Christian, M.C., Gwyther, S.G. (2000) J Natl Cancer Inst 92, 205-16)

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

Results posted on

2019-08-16

Participant Flow

Pre-treatment Evaluation: Following informed consent, patients will be scheduled for a biopsy of accessible tumor. The specimen will be assessed for p53 status by sequencing and S100B, p53, and p21 expression

Participant milestones

Participant milestones
Measure	Treatment Arm Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=6 Participants Patients will receive 4 mg/kg/day IV pentamidine isethionate infused slowly over 2 hours on each treatment day. Each treatment cycle will consist of 2 weeks of therapy, five days per week, followed by 2 weeks of observation.
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months

Population: Six participants analyzed.

Outcome measures

Outcome measures
Measure	Pentamidine n=6 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Response Rate in Patients Treated With Pentamidine	0 Participants

SECONDARY outcome

Timeframe: Pre-Study, an average of 12 days

Population: Only data for 1 site was analyzed for this outcome measure

Core Needle Tumor Biopsy

Outcome measures

Outcome measures
Measure	Pentamidine n=4 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1	3 Participants

SECONDARY outcome

Timeframe: Day 12 Cycle 1

Population: Only 1 participant from 1 site had a biopsy collected and analyzed

Core needle tumor biopsy - at Day 12 at first cycle of treatment

Outcome measures

Outcome measures
Measure	Pentamidine n=1 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure	1 Participants

SECONDARY outcome

Timeframe: Pre-Study

Population: Only data for 1 site was analyzed for this outcome measure.

Serum for S100B

Outcome measures

Outcome measures
Measure	Pentamidine n=4 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Expression of S100B Pre Pentamidine Exposure	332.5 pg/ml Interval 116.5 to 5090.0

SECONDARY outcome

Timeframe: Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12

Population: Only data from 1 site was analyzed for this outcome measure

Serum for S100B level

Outcome measures

Outcome measures
Measure	Pentamidine n=4 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Expression of S100B C1D8	450 pg/ml Interval 88.1 to 5679.0
Expression of S100B C1D12	137 pg/ml Interval 74.0 to 5409.0
Expression of S100B C2D8	142.1 pg/ml Interval 125.0 to 159.2
Expression of S100B C2D12	150 pg/ml Interval 150.0 to 150.0

SECONDARY outcome

Timeframe: Up to 6 months

Metabolic Panel, Physical Exam, Vitals

Outcome measures

Outcome measures
Measure	Pentamidine n=6 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Number of Participants With Serious and Non Serious Adverse Events	6 Participants

SECONDARY outcome

Timeframe: Every 8 weeks, assesed up to 6 months

Population: Only data for 1 site was analyzed for this outcome measure.

Radiologic intervention using RECIST (x-ray, CT, MRI) Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.

Outcome measures

Outcome measures
Measure	Pentamidine n=3 Participants Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Time to Progression	36 days Interval 36.0 to 51.0

Adverse Events

Treatment Arm

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Arm n=6 participants at risk Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Metabolism and nutrition disorders Hypoglycemia	16.7% 1/6 • Number of events 1
Infections and infestations Infection	16.7% 1/6 • Number of events 1

Other adverse events

Other adverse events
Measure	Treatment Arm n=6 participants at risk Pentamidine isethionate will be administered at a dose of 4 mg/kg/day over 120 minutes each day, Monday - Friday for two weeks followed by a drug free period of 2 weeks.
Gastrointestinal disorders Anorexia	33.3% 2/6 • Number of events 2
Psychiatric disorders Anxiety	33.3% 2/6 • Number of events 2
Renal and urinary disorders Blood in urine	33.3% 2/6 • Number of events 2
Renal and urinary disorders Creatinine	33.3% 2/6 • Number of events 4
Blood and lymphatic system disorders Deep vein thrombosis	16.7% 1/6 • Number of events 1
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Dry heaves	16.7% 1/6 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 2
Blood and lymphatic system disorders Edema	16.7% 1/6 • Number of events 2
Skin and subcutaneous tissue disorders Erythema	16.7% 1/6 • Number of events 2
General disorders Fatigue	50.0% 3/6 • Number of events 3
General disorders Headache	16.7% 1/6 • Number of events 1
Cardiac disorders Heart palpitation	16.7% 1/6 • Number of events 1
Metabolism and nutrition disorders Hyperglycemia	33.3% 2/6 • Number of events 8
General disorders Hypoalbuminemia	16.7% 1/6 • Number of events 1
General disorders Hypokalemia	16.7% 1/6 • Number of events 1
Metabolism and nutrition disorders Hypoglycemia	50.0% 3/6 • Number of events 6
General disorders Hypotension	33.3% 2/6 • Number of events 3
Gastrointestinal disorders Increase in GERD symptoms	16.7% 1/6 • Number of events 1
General disorders Infiltration	16.7% 1/6 • Number of events 2
General disorders Insomnia	16.7% 1/6 • Number of events 1
Vascular disorders Intermittent hypotension	16.7% 1/6 • Number of events 2
General disorders Malaise	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Metallic taste in mouth	16.7% 1/6 • Number of events 1
General disorders Nausea	50.0% 3/6 • Number of events 5
Blood and lymphatic system disorders Neutropenia	16.7% 1/6 • Number of events 1
Nervous system disorders Numbness of the face	16.7% 1/6 • Number of events 2
General disorders Proteinuria	33.3% 2/6 • Number of events 3
Skin and subcutaneous tissue disorders Rash	16.7% 1/6 • Number of events 1
Blood and lymphatic system disorders Reduced hemoglobin	16.7% 1/6 • Number of events 1
Respiratory, thoracic and mediastinal disorders Sinus congestion	16.7% 1/6 • Number of events 1
Cardiac disorders Sinus tachycardia	33.3% 2/6 • Number of events 2
General disorders Upper back pain	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 2
General disorders Weakness	33.3% 2/6 • Number of events 2
Skin and subcutaneous tissue disorders Wound re-open	16.7% 1/6 • Number of events 1

Additional Information

Edward A. Sausville, M.D., Ph.D.

University of Maryland Greenebaum Cancer Center

Phone: 410-328-7394

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place