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

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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:
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
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Olaparib With C225 and Radiation Therapy
Hide 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
Arm/Group Title Olaparib With C225 and Radiation Therapy
Hide 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
Hide 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%
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of Olaparib
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Olaparib With C225 and Radiation Therapy
Hide 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
Time Frame 6 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Olaparib With C225 and Radiation Therapy
Hide 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%)    
Hide 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.
Hide 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
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
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
Layout table for Results Point of Contact information
Name/Title: Dr. David Raben
Organization: University of Colorado, Denver
Phone: 303-724-3027
EMail: david.raben@ucdenver.edu
Layout table for additonal information
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