Trial Outcomes & Findings for A Study of Carboplatin, Cetuximab and RAD001 in Advanced Head and Neck Cancer (NCT NCT01283334)
NCT ID: NCT01283334
Last Updated: 2014-12-04
Results Overview
This phase 1 clinical trial used a standard 3 + 3 design. Four dose levels of everolimus were planned to be evaluated, and the standard 3 + 3 design with dose de-escalation was used in the trial. Namely, 3 patients were assigned to starting dose level 1. If no dose-limiting toxicity (DLT) was observed, the trial proceeded to the next dose level, and another cohort of 3 patients was enrolled. If at least 2 of the 3 patients experienced at least 1 DLT, then the dose level decreased; otherwise, if only 1 patient experienced DLT, then 3 more patients were enrolled at the same dose level. If none of the 3 additional patients experienced DLT, the dose was escalated; otherwise, the dose level decreased. Dose reduction continued until a dose level was reached at which 6 patients had been treated and at most 1 DLT was observed.
COMPLETED
PHASE1/PHASE2
20 participants
Within the first 21 days of therapy
2014-12-04
Participant Flow
After institutional review board approval, the study enrolled 20 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN).
Participant milestones
| Measure |
Carboplatin, Cetuximab and Everolimus
Carboplatin, cetuximab and RAD001 (everolimus)
Carboplatin, cetuximab and RAD001: For phase I, dose escalation will be 2.5mg, 5mg, 7.5mg or 10mg given orally on a daily basis
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Carboplatin, Cetuximab and Everolimus
Carboplatin, cetuximab and RAD001 (everolimus)
Carboplatin, cetuximab and RAD001: For phase I, dose escalation will be 2.5mg, 5mg, 7.5mg or 10mg given orally on a daily basis
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Inability to Swallow Everolimus Pills
|
1
|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
A Study of Carboplatin, Cetuximab and RAD001 in Advanced Head and Neck Cancer
Baseline characteristics by cohort
| Measure |
Carboplatin, Cetuximab and Everolimus
n=20 Participants
Carboplatin, cetuximab and RAD001 (everolimus)
Carboplatin, cetuximab and RAD001: For phase I, dose escalation will be 2.5mg, 5mg, 7.5mg or 10mg given orally on a daily basis
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within the first 21 days of therapyThis phase 1 clinical trial used a standard 3 + 3 design. Four dose levels of everolimus were planned to be evaluated, and the standard 3 + 3 design with dose de-escalation was used in the trial. Namely, 3 patients were assigned to starting dose level 1. If no dose-limiting toxicity (DLT) was observed, the trial proceeded to the next dose level, and another cohort of 3 patients was enrolled. If at least 2 of the 3 patients experienced at least 1 DLT, then the dose level decreased; otherwise, if only 1 patient experienced DLT, then 3 more patients were enrolled at the same dose level. If none of the 3 additional patients experienced DLT, the dose was escalated; otherwise, the dose level decreased. Dose reduction continued until a dose level was reached at which 6 patients had been treated and at most 1 DLT was observed.
Outcome measures
| Measure |
Everolimus Dose Level 1 DLT
n=6 Participants
Carboplatin, cetuximab and RAD001 (everolimus) at Dose Level 1 (2.5 mg/day)
|
Everolimus Dose Level -1 DLT
n=6 Participants
Carboplatin, cetuximab and RAD001 (everolimus) at Dose Level -1 (2.5 mg every other day)
|
|---|---|---|
|
To Measure the Safety and Clinical Effectiveness of the Combination of Carboplatin, Cetuximab and RAD001 in Patients With Advanced (Recurrent or Metastatic) Head and Neck Cancer
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: The time of PFS was calculated as the time from study enrollment to the disease progression date, death date, or last contact, whichever came first, up to 25 monthsObjective tumor responses were assessed every 2 cycles of chemotherapy with computed tomography or positron emission tomography/ computed tomography scans in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Outcome measures
| Measure |
Everolimus Dose Level 1 DLT
n=13 Participants
Carboplatin, cetuximab and RAD001 (everolimus) at Dose Level 1 (2.5 mg/day)
|
Everolimus Dose Level -1 DLT
Carboplatin, cetuximab and RAD001 (everolimus) at Dose Level -1 (2.5 mg every other day)
|
|---|---|---|
|
Progression-free Survival (PFS)
|
8.15 months
Interval 1.0 to 37.0
|
—
|
Adverse Events
Carboplatin, Cetuximab and Everolimus
Serious adverse events
| Measure |
Carboplatin, Cetuximab and Everolimus
n=20 participants at risk
Carboplatin, cetuximab and RAD001 (everolimus)
Carboplatin, cetuximab and RAD001: For phase I, dose escalation will be 2.5mg, 5mg, 7.5mg or 10mg given orally on a daily basis
|
|---|---|
|
Gastrointestinal disorders
Nausea and vomiting
|
5.0%
1/20 • Up to 25 months
|
|
Gastrointestinal disorders
Hemoptysis and death
|
5.0%
1/20 • Up to 25 months
|
Other adverse events
| Measure |
Carboplatin, Cetuximab and Everolimus
n=20 participants at risk
Carboplatin, cetuximab and RAD001 (everolimus)
Carboplatin, cetuximab and RAD001: For phase I, dose escalation will be 2.5mg, 5mg, 7.5mg or 10mg given orally on a daily basis
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
35.0%
7/20 • Up to 25 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
5/20 • Up to 25 months
|
|
Immune system disorders
Anaphylaxis
|
20.0%
4/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Hypokalemia
|
20.0%
4/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
20.0%
4/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Hypophosphatemia
|
30.0%
6/20 • Up to 25 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.0%
3/20 • Up to 25 months
|
|
General disorders
Fatigue
|
10.0%
2/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Hyponatremia
|
10.0%
2/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Anemia
|
5.0%
1/20 • Up to 25 months
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia
|
5.0%
1/20 • Up to 25 months
|
|
Gastrointestinal disorders
Diarrhea
|
5.0%
1/20 • Up to 25 months
|
|
Infections and infestations
Sepsis
|
5.0%
1/20 • Up to 25 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.0%
1/20 • Up to 25 months
|
|
Skin and subcutaneous tissue disorders
Mucositis
|
15.0%
3/20 • Up to 25 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place