Gemcitabine and Docetaxel in Treating Patients With Persistent, Recurrent, or Metastatic Head and Neck Cancer

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00248560
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 89
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gemcitabine together with docetaxel works in treating patients with persistent, recurrent, or metastatic head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: docetaxel; Drug: Gemcitabine	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate in patients with previously treated persistent, recurrent, or metastatic squamous cell carcinoma of the head and neck treated with gemcitabine and docetaxel.

Secondary

• Determine the toxicity of this regimen in these patients.

• Determine the duration of response and survival of patients treated with this regimen.

OUTLINE: Patients receive gemcitabine IV over 30 minutes and docetaxel IV over 60 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 4 additional courses of therapy beyond documentation of CR.

After completion of study treatment, patients are followed for survival.

PROJECTED ACCRUAL: A total of 17-41 patients will be accrued within 42-49 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Gemcitabine and Docetaxel (GEMDOC) Combination in Patients With Previously Treated Recurrent or Metatstatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine, docetaxel Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.	Drug: docetaxel; Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.; Other Names: Taxotere ; Drug: Gemcitabine; Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Response (Complete Response [CR] + Partial Response [PR]) [every 8 weeks for approximately 8 - 48 weeks]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Response Duration [Every 8 weeks]

   Response duration in months

2. Survival [Every 8 weeks]

   Overall Survival using the Kaplan-Meier method

3. Toxicity as Measured by Number and Grade of Adverse Events [Every 2 weeks]

   Toxicity as the total number of participants with a given grade 3 and/or grade 4 adverse event

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck

• Metastatic, persistent, or recurrent disease

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Must have had definitive surgery and/or radiation therapy AND received at least 1, but no more than 2, chemotherapy regimens, either given as primary therapy or adjuvant therapy before or after surgery and/or radiotherapy

• No active or prior CNS metastasis

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• SWOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Granulocyte count > 1,500/mm^3

• Hemoglobin ≥ 8 g/dL

• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin normal

• Meets 1 of the following criteria:

• Alkaline phosphatase (AP) normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)

• AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN

• AP ≤ 5 times ULN AND AST or ALT normal

Renal

• Creatinine < 1.5 mg/dL

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• No peripheral neuropathy ≥ grade 2

• No active infection requiring systemic therapy

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or any other site

• No history of severe hypersensitivity reaction to study drugs or other drugs formulated with polysorbate 80

• No other serious condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

• No prior taxane or gemcitabine

• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics

Other

• No other concurrent therapy for this disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ammar Sukari, M.D., Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Ammar Sukari, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00248560
• Other Study ID Numbers: CDR0000445589; P30CA022453; WSU-D-2830; WSU-HIC-120904M1F
• First Posted: Nov 4, 2005
• Last Update Posted: Mar 5, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Ammar Sukari, Principal Investigator, Barbara Ann Karmanos Cancer Institute: recurrent squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; recurrent squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; metastatic squamous neck cancer with occult primary squamous cell carcinoma; recurrent metastatic squamous neck cancer with occult primary; recurrent squamous cell carcinoma of the nasopharynx; stage IV squamous cell carcinoma of the nasopharynx; recurrent squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
• Additional relevant MeSH terms: Head and Neck Neoplasms; Gemcitabine; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (8.9)
Sex: Female, Male (Count of Participants)
Female	10 27.8%
Male	26 72.2%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Response (Complete Response [CR] + Partial Response [PR])
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	every 8 weeks for approximately 8 - 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Measure Participants	36
Number [participants]	6 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gemcitabine, Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Response rate
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; 0.08 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Response Duration
Description	Response duration in months
Time Frame	Every 8 weeks

Outcome Measure Data

Analysis Population Description

Only those patients that have a recorded CR or PR

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine. docetaxel: Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine. Gemcitabine: Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Measure Participants	6
Median (80% Confidence Interval) [months]	3.2

3. Secondary Outcome

Title	Survival
Description	Overall Survival using the Kaplan-Meier method
Time Frame	Every 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Measure Participants	36
Median (95% Confidence Interval) [months]	4.2

4. Secondary Outcome

Title	Toxicity as Measured by Number and Grade of Adverse Events
Description	Toxicity as the total number of participants with a given grade 3 and/or grade 4 adverse event
Time Frame	Every 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
Measure Participants	36
Anemia	13 36.1%
Neutropenia	10 27.8%
Hyponatremia	10 27.8%
Dehydration	3 8.3%
Fatigue	3 8.3%
Dyspnea	3 8.3%
Pneumonia	3 8.3%
Thrombocytopenia	2 5.6%
Febrile neutropenia	1 2.8%
Tachycardia	1 2.8%
Syncope	1 2.8%
Fluid retention	1 2.8%
Mucositis	1 2.8%
Hyperglycemia	1 2.8%
Constipation	1 2.8%
Anorexia	1 2.8%
Vomiting	1 2.8%
Other non-hematologic toxicity	1 2.8%

Adverse Events

Arm/Group Title	Gemcitabine, Docetaxel
Arm/Group Description	Gemcitabine given 3000 mg/m2 IV over 30 minutes and Docetaxel given 60mg/m2 IV over 60 minutes. The Docetaxel should be administered after the Gemcitabine.
All Cause Mortality
	Gemcitabine, Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine, Docetaxel
	Affected / at Risk (%)	# Events
Total	25/36 (69.4%)
Blood and lymphatic system disorders
Anemia	13/36 (36.1%)	13
Neutropenia	10/36 (27.8%)	10
Thrombocytopenia	2/36 (5.6%)	2
Febrile Neutropenia	1/36 (2.8%)	1
Cardiac disorders
Tachycardia	1/36 (2.8%)	1
Gastrointestinal disorders
Mucositis	1/36 (2.8%)	1
Constipation	1/36 (2.8%)	1
Vomiting	1/36 (2.8%)	1
General disorders
Fatigue	3/36 (8.3%)	3
Metabolism and nutrition disorders
Hyponatremia	10/36 (27.8%)	10
Dehydration	3/36 (8.3%)	3
Hyperglycemia	1/36 (2.8%)	1
Anorexia	1/36 (2.8%)	1
Nervous system disorders
Syncope	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/36 (8.3%)	3
Pneumonia	3/36 (8.3%)	3
Fluid Retention	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine, Docetaxel
	Affected / at Risk (%)	# Events
Total	33/36 (91.7%)
Blood and lymphatic system disorders
Anemia	19/36 (52.8%)	19
Neutropenia	6/36 (16.7%)	6
Thrombocytopenia	15/36 (41.7%)	15
Cardiac disorders
Tachycardia	4/36 (11.1%)	4
Gastrointestinal disorders
Nausea	3/28 (10.7%)	6
Mucositis	2/36 (5.6%)	2
Constipation	2/36 (5.6%)	2
Vomiting	5/36 (13.9%)	5
General disorders
Fatigue	8/36 (22.2%)	8
Investigations
Creatinine	4/36 (11.1%)	4
Metabolism and nutrition disorders
Hyponatremia	9/36 (25%)	9
Dehydration	3/36 (8.3%)	3
Hypokalemia	7/36 (19.4%)	7
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/36 (5.6%)	2
Pneumonia	2/36 (5.6%)	2
Fluid Retention	2/36 (5.6%)	2
Skin and subcutaneous tissue disorders
Rash	2/36 (5.6%)	2
Alopecia	4/36 (11.1%)	4

Limitations/Caveats

The trial design was changed during accrual to allow for study continuation although response rate was lower than predicted. The trial was completed but it did not meet the specified end points.

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.