Study of Olaparib With Radiation Therapy and Cetuximab in Advanced Head and Neck Cancer With Heavy Smoking History

• ClinicalTrials.gov Identifier: NCT01758731
• Recruitment Status: Completed
• First Posted: January 1, 2013
• Results First Posted: September 23, 2019
• Last Update Posted: September 23, 2019
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Squamous Cell Carcinoma of the Head and Neck
• Interventions: Drug: Olaparib; Drug: Cetuximab; Radiation: Radiation Therapy
• Enrollment: 17

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Olaparib With C225 and Radiation Therapy
Arm/Group Description	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
Period Title: Overall Study
Started	17
Completed	16
Not Completed	1
Reason Not Completed
Physician Decision	1

Baseline Characteristics

Arm/Group Title		Olaparib With C225 and Radiation Therapy
Arm/Group Description		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 Number of Baseline Participants		16
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	16 participants
		60.81; (46.13 to 75.48)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants
	Female	2 12.5%
	Male	14 87.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	16 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Primary site of disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants
	Tonsil	3 18.8%
	Base of Tongue	4 25.0%
	Supraglottic Larynx	6 37.5%
	Soft Palate	1 6.3%
	Larynx other	2 12.5%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Olaparib
Description	Maximum tolerated dose (MTD) of Olaparib to be used for Phase II clinical testing.
Time Frame	10 weeks from the start of protocol therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib With C225 and Radiation Therapy
Arm/Group Description:	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 Number of Participants Analyzed	16
Measure Type: Number; Unit of Measure: mg twice daily
	50

Adverse Events

Time Frame	6 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Olaparib With C225 and Radiation Therapy
Arm/Group Description	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
All-Cause Mortality
	Olaparib With C225 and Radiation Therapy
	Affected / at Risk (%)
Total	6/16 (37.50%)
Serious Adverse Events
	Olaparib With C225 and Radiation Therapy
	Affected / at Risk (%)	# Events
Total	4/16 (25.00%)
Gastrointestinal disorders
Grade 3 mucositis † [1]	1/1 (100.00%)	1
General disorders
Feed tube placement pain † [2]	1/16 (6.25%)	1
Confusion, somnolence, disorientation, hypoxia † [3]	1/16 (6.25%)	1
Dehydration † [4]	1/16 (6.25%)	1
† Indicates events were collected by systematic assessment; [1] Subject developed sloughing and necrosis of the left pharyngeal wall 6 months post Tx. Feeding tube placed for nutritional support and tube removed at 10 months post-treatment and was able to resume normal food intake. Possibly related to study drug.; [2] Subject had an extended hospital stay after his SOC feeding tube placement due to uncontrolled pain that was caused by overeating the morning after the procedure. Not related to study drug.; [3] Subject experienced confusion, somnolence, disorientation and hypoxia on Day 10 of radiation therapy and was admitted through the Emergency Department and discharged the following day. Not related to study drug.; [4] Subject hospitalized for dehydration caused secondarily by nausea and vomiting and also diabetic ketoacidosis, acute kidney injury, anemia, hyperkalemia and hypomagnesemia. Not related to study drug.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Olaparib With C225 and Radiation Therapy
	Affected / at Risk (%)	# Events
Total	16/16 (100.00%)
Blood and lymphatic system disorders
Leukopenia †	1/16 (6.25%)
Low albumin †	1/16 (6.25%)
Lymphopenia †	3/16 (18.75%)
Ear and labyrinth disorders
Erythema †	6/16 (37.50%)
Hearing Loss †	1/16 (6.25%)
Tinnitus †	1/16 (6.25%)
Endocrine disorders
Elevated TSH †	1/16 (6.25%)
Low T4 †	1/16 (6.25%)
Gastrointestinal disorders
Anorexia †	2/16 (12.50%)
Constipation †	1/16 (6.25%)
Diarrhea †	2/16 (12.50%)
Insomnia †	1/16 (6.25%)
Mucositis †	14/16 (87.50%)
Reflux †	2/16 (12.50%)
General disorders
Chills †	2/16 (12.50%)
Dehydration †	6/16 (37.50%)
Dysgeusia †	8/16 (50.00%)
Dysphagia †	7/16 (43.75%)
Facial Swelling †	1/16 (6.25%)
Fatigue †	7/16 (43.75%)
Flatulence †	1/16 (6.25%)
Headache †	3/16 (18.75%)
Hemoptysis †	1/16 (6.25%)
Hoarseness †	3/16 (18.75%)
Hypermagnesemia †	2/16 (12.50%)
Hypokalemia †	1/16 (6.25%)
Hypomagnesemia †	5/16 (31.25%)
Hyponatremia †	1/16 (6.25%)
Infection of G-tube site †	1/16 (6.25%)
Intermittent hypocalcemia †	1/16 (6.25%)
Laryngeal Edema †	1/16 (6.25%)
Nausea †	8/16 (50.00%)
Neck Pain †	4/16 (25.00%)
Non-healing Wound †	1/16 (6.25%)
Odyophagia †	8/16 (50.00%)
Oral Pain †	3/16 (18.75%)
Otalgia †	2/16 (12.50%)
Pharynx Ulceration †	1/16 (6.25%)
Sinus Disorder †	3/16 (18.75%)
Sore Throat †	3/16 (18.75%)
Thrush †	1/16 (6.25%)
Vomiting †	7/16 (43.75%)
Weight Loss †	9/16 (56.25%)
Metabolism and nutrition disorders
Malnutrition †	4/16 (25.00%)
Skin and subcutaneous tissue disorders
Acneform rash †	8/16 (50.00%)
Dermatitis †	15/16 (93.75%)
Neck/Face Skin Infection †	1/16 (6.25%)
Pruritus †	3/16 (18.75%)
Xerosis/dry skin †	4/16 (25.00%)
Xerostomia †	9/16 (56.25%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

Tablets not crushable when patients were having difficulty swallowing; adaptive radiotherapy along with skin sparing wasn't formally incorporated into trial which might have led to less skin toxicity with cetuximab combined with olaparib

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. David Raben
• Organization: University of Colorado, Denver
• Phone: 303-724-3027
• EMail: david.raben@ucdenver.edu

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01758731
• Obsolete Identifiers: NCT01644266
• Other Study ID Numbers: 11-1658.cc
• First Submitted: December 26, 2012
• First Posted: January 1, 2013
• Results First Submitted: July 3, 2019
• Results First Posted: September 23, 2019
• Last Update Posted: September 23, 2019