Trial Outcomes & Findings for Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck (NCT NCT01133678)
NCT ID: NCT01133678
Last Updated: 2020-05-08
Results Overview
Change in tumor size (sum of longest diameters of target lesions) after two cycles of induction therapy, expressed as log of ratio of post-treatment to baseline measure.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Baseline and 2 months
Results posted on
2020-05-08
Participant Flow
Participant milestones
| Measure |
Everolimus
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
|---|---|---|
|
Overall Study
STARTED
|
25
|
25
|
|
Overall Study
COMPLETED
|
24
|
24
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Everolimus
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
|---|---|---|
|
Overall Study
Death
|
1
|
1
|
Baseline Characteristics
Study in Locally Advanced Squamous Cell Carcinoma of Head and Neck
Baseline characteristics by cohort
| Measure |
Everolimus
n=25 Participants
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
n=25 Participants
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.1 years
n=5 Participants
|
56.2 years
n=7 Participants
|
57.2 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
25 participants
n=7 Participants
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 2 monthsPopulation: One patient from each arm died prior to cycle 2 and is excluded.
Change in tumor size (sum of longest diameters of target lesions) after two cycles of induction therapy, expressed as log of ratio of post-treatment to baseline measure.
Outcome measures
| Measure |
Everolimus
n=24 Participants
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
n=24 Participants
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
|---|---|---|
|
Tumor Responses
|
-0.609 dimensionless (log ratio)
Standard Error 0.086
|
-0.796 dimensionless (log ratio)
Standard Error 0.112
|
Adverse Events
Everolimus
Serious events: 9 serious events
Other events: 22 other events
Deaths: 1 deaths
Placebo
Serious events: 11 serious events
Other events: 21 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Everolimus
n=25 participants at risk
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
n=25 participants at risk
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Infections and infestations
Catheter related infection
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Cardiac disorders
Chest pain - cardiac
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
1/25 • 3 years
|
12.0%
3/25 • 3 years
|
|
Injury, poisoning and procedural complications
Dermatitis radiation
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Infections and infestations
Device related infection
|
8.0%
2/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
General disorders
Edema limbs
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.0%
1/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
General disorders
Fever
|
0.00%
0/25 • 3 years
|
16.0%
4/25 • 3 years
|
|
Cardiac disorders
Heart failure
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
4.0%
1/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Vascular disorders
Thromboembolic event
|
4.0%
1/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Gastrointestinal disorders
Colonic perforation
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
|
Infections and infestations
Lung infection
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.0%
1/25 • 3 years
|
0.00%
0/25 • 3 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/25 • 3 years
|
4.0%
1/25 • 3 years
|
Other adverse events
| Measure |
Everolimus
n=25 participants at risk
Everolimus 5 mg PO Daily for 2 21-day cycles
Everolimus: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel (175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Everolimus 5 mg PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
Placebo
n=25 participants at risk
Placebo 5 mg PO Daily for 2 21-day cycles
Placebo: Phase II Portion (2 21-day cycles of induction therapy) Cisplatin (75 mg/m2 day 1) Paclitaxel(175 mg/m2, day 1) Cetuximab(400 mg/m2 loading dose day 1 then 250mg/m2 weekly ) Placebo PO daily. Following induction patients received \[paclitaxel (100 mg/m2 IV weekly), 5-FU (600 mg/m2 IV day 1-5), hydroxyurea 500 mg BID PO (day 1-5), and hyperfractionated twice daily radiotherapy (150 cGy per fraction) day 1-5 of a 14 day cycle which is repeated to deliver the prescribed radiotherapy dose.
|
|---|---|---|
|
Infections and infestations
Alanine aminotransferase increased
|
12.0%
3/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
32.0%
8/25 • 3 years
|
32.0%
8/25 • 3 years
|
|
Blood and lymphatic system disorders
Anemia
|
8.0%
2/25 • 3 years
|
16.0%
4/25 • 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
68.0%
17/25 • 3 years
|
56.0%
14/25 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
12.0%
3/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
General disorders
Chills
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Gastrointestinal disorders
Constipation
|
60.0%
15/25 • 3 years
|
60.0%
15/25 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
16.0%
4/25 • 3 years
|
16.0%
4/25 • 3 years
|
|
Injury, poisoning and procedural complications
Dermatitis radiation
|
72.0%
18/25 • 3 years
|
80.0%
20/25 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
32.0%
8/25 • 3 years
|
36.0%
9/25 • 3 years
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Gastrointestinal disorders
Dysphagia
|
24.0%
6/25 • 3 years
|
24.0%
6/25 • 3 years
|
|
General disorders
Fatigue
|
80.0%
20/25 • 3 years
|
80.0%
20/25 • 3 years
|
|
General disorders
Fever
|
4.0%
1/25 • 3 years
|
12.0%
3/25 • 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
8.0%
2/25 • 3 years
|
16.0%
4/25 • 3 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
28.0%
7/25 • 3 years
|
20.0%
5/25 • 3 years
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Infections and infestations
Mucosal infection
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
80.0%
20/25 • 3 years
|
80.0%
20/25 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
64.0%
16/25 • 3 years
|
68.0%
17/25 • 3 years
|
|
Gastrointestinal disorders
Oral pain
|
44.0%
11/25 • 3 years
|
48.0%
12/25 • 3 years
|
|
General disorders
Pain
|
24.0%
6/25 • 3 years
|
20.0%
5/25 • 3 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
12.0%
3/25 • 3 years
|
20.0%
5/25 • 3 years
|
|
Investigations
Platelet count decreased
|
24.0%
6/25 • 3 years
|
8.0%
2/25 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
84.0%
21/25 • 3 years
|
68.0%
17/25 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/25 • 3 years
|
12.0%
3/25 • 3 years
|
|
Gastrointestinal disorders
Vomiting
|
16.0%
4/25 • 3 years
|
36.0%
9/25 • 3 years
|
|
Investigations
Weight loss
|
8.0%
2/25 • 3 years
|
16.0%
4/25 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place