Cetuximab + Taxotere With Low Dose Fractionated Radiation for Head and Neck Carcinoma

• Sponsor: University of Miami (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01794845
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 36.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Whether low-dose radiation in addition to Taxotere and Erbitux improves the response rate of patients with recurrent unresectable head and neck squamous cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma; Head and Neck Cancer; Recurrent Disease	Drug: Erbitux; Drug: Taxotere; Radiation: Low Dose Fractionated Radiation Therapy	Phase 2

Detailed Description

The investigator's approach is based on the following reasons:

• Low dose hyper-radiation sensitivity response will be significantly enhanced in Taxotere- induced G2/M cell cycle arrest.

• LDFRT will render enhanced bax activation mediated mode of cell death.

• Erbitux will arrest the cells in G1/G0 phase leading to p21-mediated mode of cell death.

• The toxicity profile is expected to be minimal.

Based on the above mentioned reasons, we propose this novel schema of treatment in recurrent SCCHN.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial Using Erbitux+ Taxotere With Low Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck Carcinoma
• Actual Study Start Date: Jun 3, 2013
• Actual Primary Completion Date: Jun 7, 2016
• Actual Study Completion Date: Jun 7, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Erbitux, Taxotere, LD Fractionated RT Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT)

Drug: Erbitux; Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere.; Other Names: Cetuximab ; Drug: Taxotere; Taxotere : 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7.; Other Names: Docetaxel ; Radiation: Low Dose Fractionated Radiation Therapy; Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.; Other Names: LDFRT

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) of Participants [Up to 6 months from End of Treatment, about 9 months]

   ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria.

Secondary Outcome Measures

1. Number of Study Participants Experiencing Treatment-Related Toxicity [Up to 6 years]

   Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: Acute toxicity is defined as toxicity occurring within 90 days of start of therapy. Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy.

2. Estimated Progression-Free Survival (PFS) [Up to 6 years]

   Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment.

3. Estimated Overall Survival (OS) [Up to 6 years]

   Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients must have pathologically confirmed recurrence (reappearance of previously cleared) squamous cell cancer primary in the upper aerodigestive tract .Patients may have experienced more than one recurrence as long as the first recurrence occurred ≥ 6 months following the end of the prior RT.

2. The recurrence must have defined bi- or uni-dimensional measurements.

3. Recurrence must be confined to the head and neck above the clavicles (loco-regional recurrence).

4. The patient must not be a candidate for surgical resection.

5. Patients must be at least 6 months from completion of prior chemotherapy and radiation therapy.

6. Patients may have received prior chemotherapy as a component of their primary treatment, but not for recurrent disease.

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

8. Granulocytes ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum bilirubin ≤ 1.5 mg/dl, creatinine < 1.5 mg/dl within 3 weeks prior to registration.

9. Liver Function Tests (LFTs) ≤ 2 x normal (serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic-pyruvic transaminase (SGPT)/Alkaline Phosphatase). If > 2 x normal, liver ultrasound or CT is required to exclude metastases. If negative for metastases, patients are eligible.

10. Patients must sign a study-specific informed consent form prior to study entry.

Exclusion Criteria:

1. Distant metastases outside of the head and neck.

2. Primary disease in the nasopharynx or the salivary gland.

3. Other concurrent invasive malignancies.

4. Prior invasive malignancy unless disease free for at least two years (except prior in situ malignancies, e.g. cervix, breast, non-melanomatous skin cancer, etc. are permissible).

5. Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival.

6. Pre-existing grade ≥ 2 peripheral sensory neuropathy

7. Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns.

8. Prior history of sever hypersensitivity reaction to Docetaxol, Cetuximab or a drug with formulated with Polysorbate 80.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

• University of Miami

Investigators

• Principal Investigator: Matthew C Abramowitz, MD, University of Miami

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Matthew Abramowitz, Assistant Professor of Clinical, University of Miami
• ClinicalTrials.gov Identifier: NCT01794845
• Other Study ID Numbers: 20090467
• First Posted: Feb 20, 2013
• Last Update Posted: May 11, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Matthew Abramowitz, Assistant Professor of Clinical, University of Miami: SCCHN; Head and Neck Cancer; Squamous Cell Carcinoma; Recurrent
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Recurrence; Docetaxel; Cetuximab

Study Results

Participant Flow

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 40%
>=65 years	2 40%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	4 80%
Region of Enrollment (participants) [Number]
United States	5 100%
Site of Head and Neck Carcinoma (Count of Participants)
Larynx	2 40%
Floor of Mouth	1 20%
Tonsil	1 20%
Surgery (Count of Participants)
Count of Participants [Participants]	1 20%
Chemotherapy (Count of Participants)
Count of Participants [Participants]	3 60%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR) of Participants
Description	ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria.
Time Frame	Up to 6 months from End of Treatment, about 9 months

Outcome Measure Data

Analysis Population Description

Data for 4 of 5 participants analyzed due to 1 subject withdrawing prior to receiving protocol therapy.

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Measure Participants	4
Overall Response (CR+PR), 1 month	50 1000%
Overall Response (CR+PR), 6 months	0 0%
Complete Response (CR), 1 month	0 0%
Complete Response (CR), 6 months	0 0%
Partial Response (PR), 1 month	50 1000%
Partial Response (PR), 6 months	0 0%
Stable Disease (SD), 1 month	25 500%
Stable Disease (SD), 6 months	0 0%
Progressive Disease (PD), 1 month	25 500%
Progressive Disease (PD), 6 months	100 2000%

2. Secondary Outcome

Title	Number of Study Participants Experiencing Treatment-Related Toxicity
Description	Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: Acute toxicity is defined as toxicity occurring within 90 days of start of therapy. Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

Data for 4 of 5 participants analyzed due to 1 subject withdrawing prior to receiving protocol therapy.

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Measure Participants	4
Acute Toxicities	4 80%
Late Toxicities	0 0%

3. Secondary Outcome

Title	Estimated Progression-Free Survival (PFS)
Description	Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

At the time of study termination in June 2016, 1 patient had already died, 1 patient had refused follow-up, 1 patient was lost to follow-up and 1 patient was alive with disease. Progression-free survival data were not analyzed due to an insufficient number of evaluable participants accrued and early study termination for lack of efficacy.

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Measure Participants	0

4. Secondary Outcome

Title	Estimated Overall Survival (OS)
Description	Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations).
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

At the time of study termination in June 2016, 1 patient had already died, 1 patient had refused follow-up, 1 patient was lost to follow-up and 1 patient was alive with disease. Overall survival data were not analyzed due to an insufficient number of evaluable participants accrued and early study termination for lack of efficacy.

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
Measure Participants	0

Adverse Events

Arm/Group Title	Erbitux, Taxotere, LD Fractionated RT
Arm/Group Description	Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT): Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere. Taxotere: 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7. Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.
All Cause Mortality
	Erbitux, Taxotere, LD Fractionated RT
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Serious Adverse Events
	Erbitux, Taxotere, LD Fractionated RT
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Vascular disorders
Hematoma	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Erbitux, Taxotere, LD Fractionated RT
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Anemia	1/4 (25%)	2
Ear and labyrinth disorders
Ear pain	1/4 (25%)	1
Gastrointestinal disorders
Constipation	1/4 (25%)	1
Dehydration	1/4 (25%)	1
Dry mouth/salivary gland (xerostomia)	2/4 (50%)	2
Dysphagia	2/4 (50%)	2
General disorders
Insomnia	1/4 (25%)	1
Pain	1/4 (25%)	2
Infections and infestations
Paronychia	1/4 (25%)	1
Injury, poisoning and procedural complications
Dermatitis radiation	1/4 (25%)	1
Investigations
Lymphocyte count decreased	1/4 (25%)	1
Metabolism and nutrition disorders
Hyperkalemia	1/4 (25%)	4
Hypermagnesemia	1/4 (25%)	1
Hypoalbuminemia	1/4 (25%)	1
Nervous system disorders
Dysgeusia	1/4 (25%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/4 (25%)	2
Pruritus	1/4 (25%)	1
Rash acneiform	3/4 (75%)	7
Skin induration	1/4 (25%)	1

Limitations/Caveats

Data analyzed for 4 out of 5 study participants due to 1 study participant withdrawing prior to receiving study therapy.

More Information

Certain Agreements

All Principal Investigators ARE 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.