Trial Outcomes & Findings for A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy In HPV-Negative HNSCC. (NCT NCT01732640)
NCT ID: NCT01732640
Last Updated: 2018-07-26
Results Overview
The maximally tolerated dose (MTD) was defined as the dose of afatinib in which \<2 of 6 patients experience a DLT with the next higher dose having at least 2 of up to 6 patients experiencing a DLT. No dose escalations or de-escalations are permitted within each subject's treatment.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
1 Year (Average)
Results posted on
2018-07-26
Participant Flow
Participant milestones
| Measure |
20 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
|
Overall Study
COMPLETED
|
6
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
20 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy In HPV-Negative HNSCC.
Baseline characteristics by cohort
| Measure |
All Study Participants
n=9 Participants
Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
|
ECOG Status
0
|
6 Participants
n=5 Participants
|
|
ECOG Status
1
|
3 Participants
n=5 Participants
|
|
Disease Site
Larynx
|
2 Participants
n=5 Participants
|
|
Disease Site
Oropharynx
|
6 Participants
n=5 Participants
|
|
Disease Site
Oral Cavity
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 Year (Average)The maximally tolerated dose (MTD) was defined as the dose of afatinib in which \<2 of 6 patients experience a DLT with the next higher dose having at least 2 of up to 6 patients experiencing a DLT. No dose escalations or de-escalations are permitted within each subject's treatment.
Outcome measures
| Measure |
All Study Participants
n=9 Participants
14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Maximum Tolerated Dose (MTD) of Afatinib
|
20 mg
|
—
|
PRIMARY outcome
Timeframe: After completion of 2 cycles of induction chemotherapy (at least 8 weeks)Patients were accessed for response by CT/MRI and clinical exam. Partial response was defined as a greater than 30 % reduction in tumor size.
Outcome measures
| Measure |
All Study Participants
n=7 Participants
14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Objective Tumor Response
Partial Response
|
5 Participants
|
—
|
|
Objective Tumor Response
Stable Disease
|
2 Participants
|
—
|
PRIMARY outcome
Timeframe: 1 year (average)Grade 3 or 4 neutropenia (ie. absolute neutrophil count \<1000 cells/mm\^3) that was associated with a fever\>38.5 degrees C or lasting longer than 5 days, grade 3 thrombocytopenia with bleeding or grade 4 thrombocytopenia, and any grade 3 or 4 non-hematologic toxicity per CTCAE criteria which were probably or definitely related to study therapy. During the chemoradiation, an event of stomatitis, pharyngitis, mucositis, or dermatitis was not considered to be a dose limiting toxicity unless it was a grade 4 that did resolve to \<grade 2 with a radiation treatment break (not to exceed 10 days) or with withholding chemotherapy (not to exceed 2 weekly doses).
Outcome measures
| Measure |
All Study Participants
n=6 Participants
14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
n=3 Participants
Eligible patients will begin a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Number of Participants With Dose Limiting Toxicities
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 5 YearsPopulation: Patients were taken off study before the full 5 years could be completed, therefore data was not collected for this outcome measure.
To estimate the overall response rate after completion of chemoradiation.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 YearsPopulation: Patients were taken off study before the full 2 years could be completed, therefore data was not collected for this outcome measure.
To estimate the 2 year progression free survival.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 YearsPopulation: Patients were taken off study before the full 2 years could be completed, therefore data was not collected for this outcome measure.
To estimate the median overall survival.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 YearsPopulation: Patients were taken off study before the full 5 years could be completed, therefore data was not collected for this outcome measure.
To estimate the biological marker activity of afatinib by serial sampling of tumor and blood samples from patients, and correlate with clinical and pathological response and outcomes. On- and off-target effects of afatinib will be assessed for the biological marker activity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 YearsPopulation: Patients were taken off study before the full 5 years could be completed, therefore data was not collected for this outcome measure.
To estimate the activity of afatinib by obtaining serial FLT-PET/CT and DW-MRI, And compare to standard of care CT images (which will be acquired at baseline and at the completion of treatment, and categorized per RECIST criteria) and correlated with response.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 YearsPopulation: Patients were taken off study before the full 5 years could be completed, therefore data was not collected for this outcome measure.
To correlate the response with standard imaging CT/MRI and FDG PET pre and post treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 yearsPopulation: Patients were taken off study before the full 5 years could be completed, therefore data was not collected for this outcome measure.
To estimate the overall response rate after completion of chemoradiation
Outcome measures
Outcome data not reported
Adverse Events
20 mg Afatinib
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
30 mg Afatinib
Serious events: 3 serious events
Other events: 0 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
20 mg Afatinib
n=6 participants at risk
Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
30 mg Afatinib
n=3 participants at risk
Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
|
|---|---|---|
|
Blood and lymphatic system disorders
Gr. 4 Neutropenia
|
16.7%
1/6 • Number of events 1
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
0.00%
0/3
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Blood and lymphatic system disorders
Gr. 3 Elevated ALT
|
16.7%
1/6 • Number of events 1
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
0.00%
0/3
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Respiratory, thoracic and mediastinal disorders
Gr. 3 Pneumonia
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
66.7%
2/3 • Number of events 2
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Gastrointestinal disorders
Gr. 3 Abdominal Pain
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
66.7%
2/3 • Number of events 2
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Gastrointestinal disorders
Gr. 3 Diarrhea
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
33.3%
1/3 • Number of events 1
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Blood and lymphatic system disorders
Gr. 3 Pancytopenia
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
66.7%
2/3 • Number of events 2
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Infections and infestations
Gr. 3 Urinary Tract Infection
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
33.3%
1/3 • Number of events 1
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
|
Infections and infestations
Gr. 4 Sepsis
|
0.00%
0/6
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
66.7%
2/3 • Number of events 2
Only Grade 3-5 Serious Adverse Events were monitored and assessed.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place