Trial Outcomes & Findings for Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors (NCT NCT02689219)
NCT ID: NCT02689219
Last Updated: 2019-12-10
Results Overview
Measured by RECIST v1.1 and tumor markers (AFP and BhCG). CR - disappearance of all target lesions and normalization of serum tumor markers for at least 4 weeks. When only evidence of disease is elevated serum tumor markers, then values must fall below the upper limit of normal for the assay and remain at that level for at least 4 weeks. PR - at least a 30% decrease in the sum of the diameters of target lesions compared to the baseline sum diameters for at least 2 measurements 1 month apart with the serum markers as stable/decreasing. When only evidence of disease is elevated serum tumor markers, then values must fall \>=90% below baseline pretreatment levels for BhCG or 50% decrease below baseline pretreatment levels for AFP and persist for 6 weeks. If both tumor markers are elevated and one falls below 90% the other should fall at least below 50% of baseline pretreatment levels.The percent of patients with objective response and its 95% exact confidence interval will be provided.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Up to 1 year
Results posted on
2019-12-10
Participant Flow
This protocol was a two cohort Phase II study. A Simon two-stage design was used. One cohort (CD30 negative/unknown) met the stopping rule for lack of efficacy at the first stage interim analysis. The first stage of the second cohort (CD30 positive) was not completed because the study was stopped early due to lack of funding.
Participant milestones
| Measure |
CD30 Negative/Unknown
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
7
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
11
|
7
|
Reasons for withdrawal
| Measure |
CD30 Negative/Unknown
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Disease Progression
|
10
|
6
|
Baseline Characteristics
Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors
Baseline characteristics by cohort
| Measure |
CD30 Negative/Unknown
n=11 Participants
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 Participants
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
38.2 years
STANDARD_DEVIATION 9.09 • n=5 Participants
|
32.2 years
STANDARD_DEVIATION 9.18 • n=7 Participants
|
35.9 years
STANDARD_DEVIATION 9.35 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 1 yearPopulation: All patients who received at least one dose of study medication and at least one evaluable assessment after treatment.
Measured by RECIST v1.1 and tumor markers (AFP and BhCG). CR - disappearance of all target lesions and normalization of serum tumor markers for at least 4 weeks. When only evidence of disease is elevated serum tumor markers, then values must fall below the upper limit of normal for the assay and remain at that level for at least 4 weeks. PR - at least a 30% decrease in the sum of the diameters of target lesions compared to the baseline sum diameters for at least 2 measurements 1 month apart with the serum markers as stable/decreasing. When only evidence of disease is elevated serum tumor markers, then values must fall \>=90% below baseline pretreatment levels for BhCG or 50% decrease below baseline pretreatment levels for AFP and persist for 6 weeks. If both tumor markers are elevated and one falls below 90% the other should fall at least below 50% of baseline pretreatment levels.The percent of patients with objective response and its 95% exact confidence interval will be provided.
Outcome measures
| Measure |
CD30 Negative/Unknown
n=10 Participants
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=6 Participants
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Objective Response (Percent of Patients With Complete Response or Partial Response)
|
0 percentage of patients
There were no patients who achieved CR or PR. The confidence interval could not be estimated.
|
0 percentage of patients
There were no patients who achieved CR or PR. The confidence interval could not be estimated.
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: All patients who received at least one dose of study medication.
Duration of time from the start of treatment to time of documented progression or death. Patients who did not progress or die were censored on their last evaluation date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Outcome measures
| Measure |
CD30 Negative/Unknown
n=11 Participants
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 Participants
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Progression Free Survival
|
1.38 months
Interval 0.0 to 2.07
|
1.15 months
Interval 0.92 to 2.11
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: All patients who received at least one dose of study medication.
Duration of time from the start of treatment to time of death due to any causes. Patients who did not die were censored on their last known alive date. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Outcome measures
| Measure |
CD30 Negative/Unknown
n=11 Participants
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 Participants
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Overall Survival
|
5.89 months
Interval 1.64 to 8.19
|
2.53 months
Interval 1.12 to 12.89
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: All patients who received at least one dose of study medication.
Number of unique patients who had a treatment related (possible, probable or definite) adverse event with grade \>= 3 using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome measures
| Measure |
CD30 Negative/Unknown
n=11 Participants
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 Participants
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
|
0 Participants
|
2 Participants
|
Adverse Events
CD30 Negative/Unknown
Serious events: 2 serious events
Other events: 11 other events
Deaths: 8 deaths
CD30 Positive
Serious events: 3 serious events
Other events: 7 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
CD30 Negative/Unknown
n=11 participants at risk
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 participants at risk
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Death NOS
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Infusion related reaction
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Sudden death NOS
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Infections and infestations
Lung infection
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Nervous system disorders
Presyncope
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/11 • Up to 1 year
|
28.6%
2/7 • Up to 1 year
|
Other adverse events
| Measure |
CD30 Negative/Unknown
n=11 participants at risk
Brentuximab Vedotin 1.8 mg/kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Negative/Unknown cohort.
|
CD30 Positive
n=7 participants at risk
Brentuximab Vedotin 1.8 mg/ kg (1.2 mg/kg in patients with grade 2 peripheral neuropathy at enrollment) administered by IV infusion given over approximately 30 minutes on Day 1 of each 21-day cycle for CD30 Positive cohort.
|
|---|---|---|
|
Nervous system disorders
Peripheral motor neuropathy
|
9.1%
1/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
72.7%
8/11 • Up to 1 year
|
42.9%
3/7 • Up to 1 year
|
|
Psychiatric disorders
Anxiety
|
18.2%
2/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Psychiatric disorders
Depression
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Psychiatric disorders
Psychiatric disorders - Other
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
9.1%
1/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.2%
2/11 • Up to 1 year
|
28.6%
2/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.1%
1/11 • Up to 1 year
|
42.9%
3/7 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
36.4%
4/11 • Up to 1 year
|
28.6%
2/7 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/11 • Up to 1 year
|
28.6%
2/7 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
27.3%
3/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Vascular disorders
Hot flashes
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Vascular disorders
Hypotension
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Nervous system disorders
Paresthesia
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Gastrointestinal disorders
Nausea
|
45.5%
5/11 • Up to 1 year
|
42.9%
3/7 • Up to 1 year
|
|
Gastrointestinal disorders
Vomiting
|
27.3%
3/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Chills
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Fatigue
|
54.5%
6/11 • Up to 1 year
|
57.1%
4/7 • Up to 1 year
|
|
General disorders
Infusion related reaction
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
General disorders
Pain
|
27.3%
3/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Infections and infestations
Papulopustular rash
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Investigations
Cholesterol high
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Investigations
Weight loss
|
18.2%
2/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Metabolism and nutrition disorders
Anorexia
|
36.4%
4/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
18.2%
2/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
18.2%
2/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Nervous system disorders
Dizziness
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Nervous system disorders
Dysphasia
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Nervous system disorders
Headache
|
27.3%
3/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Nervous system disorders
Nervous system disorders - Other
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
18.2%
2/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
|
Ear and labyrinth disorders
Hearing impaired
|
18.2%
2/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Ear and labyrinth disorders
Tinnitus
|
36.4%
4/11 • Up to 1 year
|
71.4%
5/7 • Up to 1 year
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Gastrointestinal disorders
Constipation
|
36.4%
4/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
9.1%
1/11 • Up to 1 year
|
0.00%
0/7 • Up to 1 year
|
|
Gastrointestinal disorders
Dyspepsia
|
9.1%
1/11 • Up to 1 year
|
14.3%
1/7 • Up to 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place