Trial Outcomes & Findings for Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History (NCT NCT01758731)
NCT ID: NCT01758731
Last Updated: 2019-09-23
Results Overview
Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
17 participants
Primary outcome timeframe
10 weeks from the start of protocol therapy
Results posted on
2019-09-23
Participant Flow
Participant milestones
| Measure |
Olaparib With C225 and Radiation Therapy
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Olaparib With C225 and Radiation Therapy
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History
Baseline characteristics by cohort
| Measure |
Olaparib With C225 and Radiation Therapy
n=16 Participants
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
Age, Continuous
|
60.81 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Primary site of disease
Tonsil
|
3 Participants
n=99 Participants
|
|
Primary site of disease
Base of Tongue
|
4 Participants
n=99 Participants
|
|
Primary site of disease
Supraglottic Larynx
|
6 Participants
n=99 Participants
|
|
Primary site of disease
Soft Palate
|
1 Participants
n=99 Participants
|
|
Primary site of disease
Larynx other
|
2 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 10 weeks from the start of protocol therapyMaximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
Outcome measures
| Measure |
Olaparib With C225 and Radiation Therapy
n=16 Participants
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Olaparib
|
50 mg twice daily
|
Adverse Events
Olaparib With C225 and Radiation Therapy
Serious events: 4 serious events
Other events: 16 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
Olaparib With C225 and Radiation Therapy
n=16 participants at risk
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
General disorders
Feed tube placement pain
|
6.2%
1/16 • Number of events 1 • 6 years
|
|
General disorders
Confusion, somnolence, disorientation, hypoxia
|
6.2%
1/16 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Grade 3 mucositis
|
100.0%
1/1 • Number of events 1 • 6 years
|
|
General disorders
Dehydration
|
6.2%
1/16 • Number of events 1 • 6 years
|
Other adverse events
| Measure |
Olaparib With C225 and Radiation Therapy
n=16 participants at risk
Patients begin taking Olaparib at the assigned dose three days prior to their first Cetuximab infusion. Patients will receive an initial dose of Cetuximab, 400 mg/m², intravenously over 120 minutes on Day 1. The initial dose of C225 will precede the start of radiation by 5-7 days. All patients will receive RT to a total dose of 69.3 Gy in 33 fractions over 6½ weeks. Weekly C225 will be administered at 250 mg/m2 in combination with daily RT. Patients will be assigned to receive Olaparib (25, 50, 100 or 200 mg bid) in combination with RT and C225. Olaparib will be taken twice daily, beginning three days prior to first scheduled C225 infusion. A further dose level of 300mg or 400mg may be considered should the 200mg Olaparib dose be well tolerated in this C225/RT combination schedule.
Olaparib: Olaparib PO (25, 50, 100 or 200 mg bid) in combination with RT and C225. BID, beginning three days prior to first C225 infusion and discontinued after RT completed.
Cetuximab: Pre-RT cet
|
|---|---|
|
Skin and subcutaneous tissue disorders
Acneform rash
|
50.0%
8/16 • 6 years
|
|
Gastrointestinal disorders
Anorexia
|
12.5%
2/16 • 6 years
|
|
General disorders
Chills
|
12.5%
2/16 • 6 years
|
|
Gastrointestinal disorders
Constipation
|
6.2%
1/16 • 6 years
|
|
General disorders
Dehydration
|
37.5%
6/16 • 6 years
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
93.8%
15/16 • 6 years
|
|
Gastrointestinal disorders
Diarrhea
|
12.5%
2/16 • 6 years
|
|
General disorders
Dysgeusia
|
50.0%
8/16 • 6 years
|
|
General disorders
Dysphagia
|
43.8%
7/16 • 6 years
|
|
Endocrine disorders
Elevated TSH
|
6.2%
1/16 • 6 years
|
|
Ear and labyrinth disorders
Erythema
|
37.5%
6/16 • 6 years
|
|
General disorders
Facial Swelling
|
6.2%
1/16 • 6 years
|
|
General disorders
Fatigue
|
43.8%
7/16 • 6 years
|
|
General disorders
Flatulence
|
6.2%
1/16 • 6 years
|
|
General disorders
Headache
|
18.8%
3/16 • 6 years
|
|
General disorders
Hemoptysis
|
6.2%
1/16 • 6 years
|
|
General disorders
Hoarseness
|
18.8%
3/16 • 6 years
|
|
General disorders
Hypermagnesemia
|
12.5%
2/16 • 6 years
|
|
General disorders
Hypokalemia
|
6.2%
1/16 • 6 years
|
|
General disorders
Hypomagnesemia
|
31.2%
5/16 • 6 years
|
|
General disorders
Hyponatremia
|
6.2%
1/16 • 6 years
|
|
General disorders
Infection of G-tube site
|
6.2%
1/16 • 6 years
|
|
Gastrointestinal disorders
Insomnia
|
6.2%
1/16 • 6 years
|
|
General disorders
Intermittent hypocalcemia
|
6.2%
1/16 • 6 years
|
|
General disorders
Laryngeal Edema
|
6.2%
1/16 • 6 years
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.2%
1/16 • 6 years
|
|
Blood and lymphatic system disorders
Low albumin
|
6.2%
1/16 • 6 years
|
|
Endocrine disorders
Low T4
|
6.2%
1/16 • 6 years
|
|
Blood and lymphatic system disorders
Lymphopenia
|
18.8%
3/16 • 6 years
|
|
Metabolism and nutrition disorders
Malnutrition
|
25.0%
4/16 • 6 years
|
|
Gastrointestinal disorders
Mucositis
|
87.5%
14/16 • 6 years
|
|
General disorders
Nausea
|
50.0%
8/16 • 6 years
|
|
General disorders
Neck Pain
|
25.0%
4/16 • 6 years
|
|
Skin and subcutaneous tissue disorders
Neck/Face Skin Infection
|
6.2%
1/16 • 6 years
|
|
General disorders
Non-healing Wound
|
6.2%
1/16 • 6 years
|
|
General disorders
Odyophagia
|
50.0%
8/16 • 6 years
|
|
General disorders
Oral Pain
|
18.8%
3/16 • 6 years
|
|
General disorders
Otalgia
|
12.5%
2/16 • 6 years
|
|
Ear and labyrinth disorders
Hearing Loss
|
6.2%
1/16 • 6 years
|
|
General disorders
Pharynx Ulceration
|
6.2%
1/16 • 6 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
18.8%
3/16 • 6 years
|
|
Gastrointestinal disorders
Reflux
|
12.5%
2/16 • 6 years
|
|
General disorders
Sinus Disorder
|
18.8%
3/16 • 6 years
|
|
General disorders
Sore Throat
|
18.8%
3/16 • 6 years
|
|
General disorders
Thrush
|
6.2%
1/16 • 6 years
|
|
Ear and labyrinth disorders
Tinnitus
|
6.2%
1/16 • 6 years
|
|
General disorders
Vomiting
|
43.8%
7/16 • 6 years
|
|
General disorders
Weight Loss
|
56.2%
9/16 • 6 years
|
|
Skin and subcutaneous tissue disorders
Xerosis/dry skin
|
25.0%
4/16 • 6 years
|
|
Skin and subcutaneous tissue disorders
Xerostomia
|
56.2%
9/16 • 6 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place