Gemcitabine and Doxorubicin in Treating Patients With Recurrent or Progressive Head and Neck Cancer

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT00509665
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 71
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and doxorubicin, 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 doxorubicin works in treating patients with recurrent or progressive head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: doxorubicin hydrochloride; Drug: gemcitabine hydrochloride	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Gemcitabine in Combination With Doxorubicin for Patients With Head and Neck Cancer
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine+doxorubicin	Drug: doxorubicin hydrochloride; given as 25mgm2 IV on days 1 and 8 of each 21-day cycle.; Drug: gemcitabine hydrochloride; given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle

Outcome Measures

Primary Outcome Measures

1. Response Rate [Every 6 weeks from the time of initial treatment for up to 8 months]

   Per Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions assessed by CT or MRI: Complete Response (CR) is the disappearance of all target lesions (TL) and non-target lesions (NTL); Partial Response (PR) is defined by either a CR of TL and stable disease (SD) in NTL or PR of TL and non-progressive disease (PD) in NTL. Response rate is the sum of CR + PR as defined above.

Secondary Outcome Measures

1. Duration of Response [Every 6 weeks for up to 8 months]

2. Progression-free Survival [Through the end of follow up, for an average of 8 months]

3. Overall Survival [From the time of initial therapy until the time of death.]

4. Number of Patients Who Had Greater Than Grade 2 Toxicity [from time of initial treatment until end of study, an average of 6 months]

5. Correlation of Cytoxocity With Cell-cycle Arrest [prior to first dose of drug and every 6 weeks up to 6 months]

6. Correlation of Cytotoxicity With Apoptosis in Cancer Cells [prior to first dose of drug and every 6 weeks for up to 6 months]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically or cytologically confirmed head and neck cancer

• Recurrent or progressive disease

• Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan

• Must have received prior platinum-based chemotherapy regimen (cisplatin or carboplatin) with or without radiotherapy, unless the patient was deemed unsuitable for platinum-based therapy due to renal dysfunction or other clinical contraindication

Exclusion criteria:

• Known brain metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• ECOG performance status (PS) ≤ 2 OR Karnofsky PS ≥ 60%

• Absolute neutrophil count ≥ 1,500/μL

• Platelets ≥ 100,000/µL

• Total bilirubin ≤ 1.5 mg/dL

• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal

• Creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 30 mL/min

• Females of reproductive potential must not plan on conceiving children during study treatment period and must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of the study

Exclusion criteria:

• Not pregnant or breastfeeding

• History of allergic reaction attributed to compounds of similar chemical or biological composition to gemcitabine hydrochloride or doxorubicin hydrochloride

• Lower than normal cardiac ejection fraction

• Patients must have an echocardiogram or MUGA scan prior to the use of study drugs

• Uncontrolled intercurrent illness that would limit compliance with study requirements including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation

• Clinical AIDS or known positive HIV serology

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Recovered from prior therapy

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• At least 30 days since prior experimental agents

• At least 4 weeks since prior radiotherapy for palliation or for the primary tumor

Exclusion criteria:

• Prior gemcitabine hydrochloride or doxorubicin hydrochloride

• Concurrent hormones or other chemotherapeutic agents, except for steroids given for adrenal failure, hormones given for non-disease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic

• Concurrent palliative radiotherapy

• Other concurrent investigational or commercial agents or therapies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

• Principal Investigator: Paul O'Brien, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00509665
• Other Study ID Numbers: CDR0000558049; MUSC-100838
• First Posted: Jul 31, 2007
• Last Update Posted: Jul 12, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Medical University of South Carolina: recurrent squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the larynx; recurrent verrucous carcinoma of the larynx; recurrent adenoid cystic carcinoma of the oral cavity; recurrent basal cell carcinoma of the lip; recurrent mucoepidermoid carcinoma of the oral cavity; recurrent squamous cell carcinoma of the lip and oral cavity; recurrent verrucous carcinoma of the oral cavity; recurrent metastatic squamous neck cancer with occult primary; recurrent lymphoepithelioma of the nasopharynx; recurrent squamous cell carcinoma of the nasopharynx; recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity; recurrent inverted papilloma of the paranasal sinus and nasal cavity; recurrent midline lethal granuloma of the paranasal sinus and nasal cavity; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity; recurrent salivary gland cancer; recurrent lymphoepithelioma of the oropharynx; recurrent squamous cell carcinoma of the oropharynx
• Additional relevant MeSH terms: Head and Neck Neoplasms; Gemcitabine; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Overall Participants	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	5 27.8%
Male	13 72.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 38.9%
White	11 61.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Per Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions assessed by CT or MRI: Complete Response (CR) is the disappearance of all target lesions (TL) and non-target lesions (NTL); Partial Response (PR) is defined by either a CR of TL and stable disease (SD) in NTL or PR of TL and non-progressive disease (PD) in NTL. Response rate is the sum of CR + PR as defined above.
Time Frame	Every 6 weeks from the time of initial treatment for up to 8 months

Outcome Measure Data

Analysis Population Description

patients who were on study at the time of response assessment

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	17
Number [participants]	4 22.2%

2. Secondary Outcome

Title	Duration of Response
Time Frame	Every 6 weeks for up to 8 months

Outcome Measure Data

Analysis Population Description

data for this endpoint was not collected

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	0

3. Secondary Outcome

Title	Progression-free Survival
Time Frame	Through the end of follow up, for an average of 8 months

Outcome Measure Data

Analysis Population Description

Only patients who had re-staging scans are included in the number of participants analyzed.

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	17
Median (95% Confidence Interval) [months]	1.6

4. Secondary Outcome

Title	Overall Survival
Time Frame	From the time of initial therapy until the time of death.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	18
Median (95% Confidence Interval) [Months]	5.6

5. Secondary Outcome

Title	Number of Patients Who Had Greater Than Grade 2 Toxicity
Time Frame	from time of initial treatment until end of study, an average of 6 months

Outcome Measure Data

Analysis Population Description

Patients who were treated on study and had greater than grade 2 toxicity.

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	18
Count of Participants [Participants]	10 55.6%

6. Secondary Outcome

Title	Correlation of Cytoxocity With Cell-cycle Arrest
Time Frame	prior to first dose of drug and every 6 weeks up to 6 months

Outcome Measure Data

Analysis Population Description

data for this endpoint was not collected

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	0

7. Secondary Outcome

Title	Correlation of Cytotoxicity With Apoptosis in Cancer Cells
Time Frame	prior to first dose of drug and every 6 weeks for up to 6 months

Outcome Measure Data

Analysis Population Description

Data for this endpoint was not collected

Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
Measure Participants	0

Adverse Events

Time Frame	Prior to each cycle while on treatment for an average of 6 months
Arm/Group Title	Gemcitabine+Doxorubicin
Arm/Group Description	doxorubicin hydrochloride: given as 25mgm2 IV on days 1 and 8 of each 21-day cycle. gemcitabine hydrochloride: given as 100mg/m2 IV over days 1 and 8 of each 21 day cycle
All Cause Mortality
	Gemcitabine+Doxorubicin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine+Doxorubicin
	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)
Blood and lymphatic system disorders
neutropenia	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine+Doxorubicin
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
neutropenia	4/18 (22.2%)	4
leukopenia	3/18 (16.7%)	3
anemia	1/18 (5.6%)	1
thrombocytopenia	1/18 (5.6%)	1
Gastrointestinal disorders
nausea	1/18 (5.6%)	1
vomitting	1/18 (5.6%)	1
dysphagia	1/18 (5.6%)	1
General disorders
fatigue	1/18 (5.6%)	1
Infections and infestations
infection	2/18 (11.1%)	2
Metabolism and nutrition disorders
hypocalcemia	1/18 (5.6%)	1
hypophosphatemia	1/18 (5.6%)	1
hyponatremia	2/18 (11.1%)	2
hypokalemia	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
cough	1/18 (5.6%)	1
Vascular disorders
DVT	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

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.