Trial Outcomes & Findings for Safety and Efficacy of Combination HDI and Anti-CTLA4 for Recurrent Inoperable Stage III or Stage IV Melanoma (NCT NCT00610857)
NCT ID: NCT00610857
Last Updated: 2017-06-22
Results Overview
Intention to treat response rate is estimated by the proportion of patients with a best response of CR, PR, or SD by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.0
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Up to 44 months
Results posted on
2017-06-22
Participant Flow
Participant milestones
| Measure |
Interferon Alfa-2b + Tremelimumab
Patients with stage IV melanoma (cutaneous, uveal, or mucosal) and measurable disease, most who had previously received therapy
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
35
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Interferon Alfa-2b + Tremelimumab
Patients with stage IV melanoma (cutaneous, uveal, or mucosal) and measurable disease, most who had previously received therapy
|
|---|---|
|
Overall Study
Not evaluable for response
|
2
|
Baseline Characteristics
Safety and Efficacy of Combination HDI and Anti-CTLA4 for Recurrent Inoperable Stage III or Stage IV Melanoma
Baseline characteristics by cohort
| Measure |
Interferon Alfa-2b + Tremelimumab
n=37 Participants
Patients treated with Tremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
|
|---|---|
|
Age, Continuous
|
56 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 44 monthsPopulation: Patients treated with Tremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
Intention to treat response rate is estimated by the proportion of patients with a best response of CR, PR, or SD by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.0
Outcome measures
| Measure |
Interferon Alfa-2b + Tremelimumab
n=37 Participants
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
|
|---|---|
|
Best Objective Response Rate (BORR)
|
24 percentage of patients
Interval 13.0 to 36.0
|
SECONDARY outcome
Timeframe: Up to 44 monthsPopulation: Patients with stage IV melanoma (cutaneous, uveal, or mucosal) and measurable disease, most who had previously received therapy
Time from initial treatment date of to date of documented progression of disease progression (TTP)
Outcome measures
| Measure |
Interferon Alfa-2b + Tremelimumab
n=37 Participants
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
|
|---|---|
|
Progression-free Survival (PFS)
|
6.4 months
Interval 3.3 to 12.1
|
SECONDARY outcome
Timeframe: Time from initial treatment date, up to 1 year1-year survival is the estimated probability of surviving one year expressed as a percent (probability of survival is not probability of dying).
Outcome measures
| Measure |
Interferon Alfa-2b + Tremelimumab
n=37 Participants
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
|
|---|---|
|
1-year Overall Survival (OS)
|
62 percentage of patients
Interval 46.0 to 78.0
|
SECONDARY outcome
Timeframe: Up to 44 monthsMedian overall survival is the (point) estimate of the time corresponding to 50% estimated probability of survival.
Outcome measures
| Measure |
Interferon Alfa-2b + Tremelimumab
n=37 Participants
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks
|
|---|---|
|
Median Overall Survival (Point Estimate)
|
21 months
Interval 9.5 to
Upper bound of the CI was not reached
|
Adverse Events
Interferon Alfa-2b + Tremelimumab (Related and Unrelated AEs)
Serious events: 15 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Interferon Alfa-2b + Tremelimumab (Related and Unrelated AEs)
n=37 participants at risk
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks per cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Pain, Abdomen NOS
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Cardiac disorders
Thyroid function, high (hyperthyroidism, thyrotoxicosis)
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Neutrophils/granulocytes (ANC/AGC)
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Vomiting
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Endocrine disorders
Renal failure
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Fatigue (asthenia, lethargy, malaise)
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Ulceration
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Thrombosis/thrombus/embolism
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Colitis
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Blood and lymphatic system disorders
Hemorrhage, CNS
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Metabolism and nutrition disorders
Supraventricular and nodal arrhythmia, Atrial fibrillation
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Diarrhea
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Bronchospasm, wheezing
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Respiratory, thoracic and mediastinal disorders
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Renal and urinary disorders
Diarrhea
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy - possibly related to cancer treatment
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Vascular disorders
GGT (gamma-Glutamyl transpeptidase)
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Vascular disorders
Encephalopathy
|
2.7%
1/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
Other adverse events
| Measure |
Interferon Alfa-2b + Tremelimumab (Related and Unrelated AEs)
n=37 participants at risk
Patients treated withTremelimumab 15 mg/kg at start of C1 + IFN-2b IV 20 MU/m2/d for 5 d/wk for 4 weeks; C2 onward- IFN-2b SQ 10MU/m2/d for 3 d/wk for 4 weeks per cycle.
|
|---|---|
|
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
10.8%
4/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
27.0%
10/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
35.1%
13/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
51.4%
19/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Cardiac disorders
Hypertension
|
8.1%
3/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Sweating (diaphoresis)
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Insomnia
|
24.3%
9/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Weight loss
|
29.7%
11/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
73.0%
27/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Rigors/chills
|
78.4%
29/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
97.3%
36/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin
|
10.8%
4/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
62.2%
23/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
70.3%
26/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Dehydration
|
8.1%
3/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Gastrointestinal
|
8.1%
3/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam), Oral cavity
|
18.9%
7/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Constipation
|
35.1%
13/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
45.9%
17/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Vomiting
|
45.9%
17/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Diarrhea
|
56.8%
21/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Anorexia
|
67.6%
25/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Gastrointestinal disorders
Nausea
|
78.4%
29/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS
|
10.8%
4/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Blood and lymphatic system disorders
Edema: limb
|
13.5%
5/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
21.6%
8/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Metabolism and nutrition disorders
CPK (creatine phosphokinase)
|
24.3%
9/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue
|
10.8%
4/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Mood alteration, Agitation
|
8.1%
3/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Neuropathy: motor
|
10.8%
4/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Neuropathy: sensory
|
13.5%
5/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Dizziness
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Mood alteration, Depression
|
18.9%
7/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Neurology
|
21.6%
8/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Nervous system disorders
Mood alteration, Anxiety
|
32.4%
12/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain, Extremity-limb
|
16.2%
6/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain - Other
|
18.9%
7/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain, Back
|
21.6%
8/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain, Abdomen NOS
|
27.0%
10/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain, Head/headache
|
32.4%
12/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
General disorders
Pain, Muscle
|
43.2%
16/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
13.5%
5/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
32.4%
12/37 • 5 years.
Includes adverse events that were considered either study treatment-related or unrelated.
|
Additional Information
Ahmad Tarhini, MD
University of Pittsburgh Cancer Institute
Phone: 4126486507
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place