Docetaxel and Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer or Other Solid Tumors

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT00390429
• Collaborator: National Cancer Institute (NCI) (NIH), Genentech, Inc. (Industry), Aventis Pharmaceuticals (Industry)
• Enrollment: 81
• Location: 1
• Arms: 3
• Duration (Months): 121
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving docetaxel together with erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with docetaxel in treating patients with solid tumors and to see how well they work in treating patients with advanced non-small cell lung cancer. (Phase I portion of the study treating patients with any solid tumor was completed as of 12/01/2004)

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: docetaxel; Drug: erlotinib hydrochloride	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the safety and feasibility of two different schedules of erlotinib hydrochloride and docetaxel in patients with advanced solid tumors. (Phase I [completed as of 12/01/2004])

• Determine the response rate in patients with advanced non-small cell lung cancer treated with second-line docetaxel and erlotinib hydrochloride. (Phase II)

Secondary

• Compare the toxicity of two different schedules of erlotinib hydrochloride and docetaxel in these patients. (Phase I [completed as of 12/01/2004])

• Determine the maximum tolerated dose of two different schedules of erlotinib hydrochloride and docetaxel. (Phase I [completed as of 12/01/2004])

• Assess the overall survival and progression-free survival. (Phase II)

• Determine the frequency and severity of toxicities associated with this treatment regimen. (Phase II)

Tertiary

• Perform laboratory correlative studies on patient tissue and blood samples to investigate potential predictors of response.

OUTLINE: This is a phase I, dose-escalation study of erlotinib hydrochloride (phase I completed as of 12/01/2004) followed by a phase II, open-label study.

• Phase I (completed as of 12/01/2004): Patients will be assigned in alternating fashion to 1 of 2 treatment groups.

• Group I: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16.

• Group II: Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16.

In both groups, treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression.

In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity.

Blood samples, buccal mucosal cells, and tumor tissue are obtained before and after treatment. Epidermal growth factor receptor (EGFR) expression and polymorphisms and p27 protein expression are assessed by immunohistochemistry. Immunofluorescence (by laser-scanning cytometry) is used to detect EGFR and p27.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Docetaxel and OSI-774 (Erlotinib) in Solid Tumor Patients With an Emphasis on NSCLC Using Molecular Correlates as Potential Markers of Response
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I, Group I (completed) Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression.	Drug: docetaxel; Given IV; Other Names: Taxotere ; Drug: erlotinib hydrochloride; Given orally; Other Names: OSI-774 Tarceva
Experimental: Phase I, Group II (completed) Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression.	Drug: docetaxel; Given IV; Other Names: Taxotere ; Drug: erlotinib hydrochloride; Given orally; Other Names: OSI-774 Tarceva
Experimental: Phase II Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity.	Drug: docetaxel; Given IV; Other Names: Taxotere ; Drug: erlotinib hydrochloride; Given orally; Other Names: OSI-774 Tarceva

Outcome Measures

Primary Outcome Measures

1. Safety and Toxicity of Erlotinib Hydrochloride and Docetaxel as Measured by NCI CTC v3.0 on Day 8 of Course 1 and on Day 1 of Every Subsequent Course (Phase I [Completed as of 12/01/2004]) [Up to 36 months]

2. Response Rate (Phase II) [Up to 36 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions and assessed by CT: 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. Comparison of Toxicity of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004]) [up to 36 months]

2. Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004]) [up to 36 months]

   Maximum tolerated dose (MTD) defined as the highest dose level at which no more than one patient experienced DLT when at least 6 patients were treated at that dose level and were assessable for toxicity, graded according to NCI CTCAE 2.0.

3. Overall Survival (Phase II) [Up to 65 months]

4. Progression-free Survival (Phase II) [Completion of study (up to 65 months)]

5. Frequency and Severity of Toxicities (Phase II) [Completion of study (up to 36 months)]

   Treatment-related adverse events Grade ≥3 by NCI CTCAE 2.0.

6. Prognostic Significance of Epithelial Growth Factor Receptor (EGFR) Expression [Completion of study (up to 36 months)]

7. Correlation of Baseline EGFR Levels With Clinical Outcome [Completion of study (up to 36 months)]

8. Correlation of Basal Levels of p27 With Response Rate and Overall Survival [Completion of study (up to 36 months)]

9. Correlation of Phospho-EGFR With Increased p27 and Clinical Outcome [Completion of study]

10. Correlation of EGFR Polymorphisms With Treatment Response and Clinical Outcome [Completion of study]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• For the phase II portion patients must have cytologically or histologically proven NSCLC. (Completed 12/1/04 - For the phase I portion of the study patients must have cytologically or histologically proven advanced solid tumors for which there is no standard therapy of curative intent).

• For the phase II portion patients must have disease that has progressed or recurred after treatment with platinum based therapy. Patients that have stable disease after front line platinum based therapy is also eligible.

• No more than 1 previous treatment for metastatic disease is allowed for the phase II portion. (Completed 12/1/04 - Any number of prior chemotherapy regimens for metastatic disease are allowed for the phase I portion).

• Patients must have measurable disease by RECIST criteria. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy. (Completed 12/1/04 - Patients with evaluable disease may be included in the phase I portion of the trial.

• Patients must be 18 years of age or older.

• Patients must have a performance status of 0-1 for the phase II portion of the trial. (Completed 12/1/04 - performance status of 0-2 for is allowed for the phase I portion of study

• Patients must have an estimated survival of at least 3 months.

• Any prior chemotherapy that patients have received has to have been completed at least 4 weeks prior to start of OSI-774/Docetaxel. For prior mitomycin chemotherapy a 6-week interval is required. Prior radiation must have been completed at least 2 weeks prior to start of therapy. All side effects must have resolved prior to start of OSI-774/Docetaxel.

• Patients must have adequate renal function as documented by a serum creatinine < 1.5 mg/dl or a calculated creatinine clearance of > 50 ml/min (see appendix for formula for calculating creatinine clearance).

• Patients must have adequate liver function as documented by serum bilirubin < ULN. AST must be < 2.5 x institutional upper limit of normal.

• Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count of

100 000/mm3.

• Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks. Because of the possibility of treatment related neurological toxicity it is difficult to evaluate for toxicity in the presence of symptomatic brain metastasis.

• All patients must give written informed consent.

• Able to take and retain oral medication.

• Patients of reproductive potential must agree to use effective contraceptive method while on treatment and for 3 months afterwards as the effects of these drugs on the unborn fetus are unknown.

• Patients on Coumadin should have their INR monitored at least once per week or more frequently depending on the investigators judgment. There have been some case reports of increased INR when Coumadin is co-administered with OSI-774/placebo.

Exclusion Criteria:

• May not have previously received docetaxel; OSI-774 or any prior EGFR targeted therapy.

• Females can not be pregnant or breastfeeding as the effects of these drugs on the unborn fetus are unknown. Documentation of a negative pregnancy test is required for all women of reproductive potential.

• Patients with symptomatic brain metastasis or still requiring steroids may not be included.

• Clinically significant ophthalmologic abnormalities will be excluded. This includes severe dry eye syndrome, keratoconjunctivitis sicca, Sjogren's syndrome, severe exposure keratopathy, or other disorders that might increase the risk of corneal epithelial injury.

• A history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80.

• Pre-existing neuropathy > grade 2 may not participate

• No other prior malignancy is allowed for the phase II portion except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for over five years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Davis Cancer Center	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis
• National Cancer Institute (NCI)
• Genentech, Inc.
• Aventis Pharmaceuticals

Investigators

• Study Chair: David R. Gandara, MD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00390429
• Other Study ID Numbers: 273721; P30CA093373; UCDCC-128; UCDCC-200311717-5; AVENTIS-Z1001055; CDR0000505821
• First Posted: Oct 19, 2006
• Last Update Posted: Dec 6, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by University of California, Davis: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; recurrent non-small cell lung cancer; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Lung Neoplasms; Docetaxel; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Phase I, Group A (1200 mg Erlotinib + 70mg/m2 Docetaxel)	Phase I, Group A (600 mg Erlotinib + 70mg/m2 Docetaxel)	Phase I, Group B (Completed)	Phase II
Arm/Group Description	Original Dose Level Patients receive docetaxel IV over 1 hour on day 1 and oral Erlotinib hydrochloride once on days 2, 9, and 16 and Docetaxel on days 1 and 22. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. Docetaxel: Given IV Erlotinib hydrochloride: Given orally	Patients receive docetaxel IV over 1 hour on day 1 and oral Erlotinib hydrochloride once on days 2, 9, and 16 and Docetaxel on days 1 and 22. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. Docetaxel: Given IV Erlotinib hydrochloride: Given orally	Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Period Title: Overall Study
STARTED	5	12	25	39
COMPLETED	5	12	25	39
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Phase I, Arm A (Completed)	Phase I, Arm B (Completed)	Phase II	Total
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally	Total of all reporting groups
Overall Participants	17	25	39	81
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	55	61	61
Sex: Female, Male (Count of Participants)
Female	6 35.3%	14 56%	24 61.5%	44 54.3%
Male	11 64.7%	11 44%	15 38.5%	37 45.7%
Race/Ethnicity, Customized (Count of Participants)
African descent	1 5.9%	0 0%	2 5.1%	3 3.7%
White	15 88.2%	23 92%	35 89.7%	73 90.1%
East/South East Asian	1 5.9%	2 8%	2 5.1%	5 6.2%
Region of Enrollment (participants) [Number]
United States	17 100%	25 100%	39 100%	81 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Toxicity of Erlotinib Hydrochloride and Docetaxel as Measured by NCI CTC v3.0 on Day 8 of Course 1 and on Day 1 of Every Subsequent Course (Phase I [Completed as of 12/01/2004])
Time Frame	Up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I, Arm A (Completed)	Phase I, Arm B (Completed)	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	17	25	39
Count of Participants [Participants]	17 100%	25 100%	39 100%

2. Primary Outcome

Title	Response Rate (Phase II)
Description	Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions and assessed by CT: 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	Up to 36 months

Outcome Measure Data

Analysis Population Description

All participants for whom response evaluation measurements were recorded at Baseline and after 2 cycles.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	39
Count of Participants [Participants]	11 64.7%

3. Secondary Outcome

Title	Comparison of Toxicity of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I, Group A (Completed)	Phase I, Group B (Completed)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	17	25
Neutropenia	10 58.8%	16 64%
Febrile neutropenia	3 17.6%	4 16%
Hemoglobin	0 0%	1 4%
Diarrhea	0 0%	3 12%
Fatigue	0 0%	1 4%
Infection (without neutropenia)	1 5.9%	3 12%
Mucositis	0 0%	1 4%
Nausea	1 5.9%	0 0%
Rash	0 0%	1 4%

4. Secondary Outcome

Title	Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
Description	Maximum tolerated dose (MTD) defined as the highest dose level at which no more than one patient experienced DLT when at least 6 patients were treated at that dose level and were assessable for toxicity, graded according to NCI CTCAE 2.0.
Time Frame	up to 36 months

Outcome Measure Data

Analysis Population Description

Phase I, arm A, MTD: erlotinib 600-1000 mg d 2, 9, and 16; and docetaxel 70 mg/m^2 d 1 on a 21-d cycle. Phase I, arm B, MTD: erlotinib 150-300 mg d 2 and 16; and docetaxel 70 mg/m^2 d 1 on a 21-d cycle.

Arm/Group Title	Phase I, Group A (Completed)	Phase I, Group B (Completed)
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally	Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	12	25
Number [mg]	600	200

5. Secondary Outcome

Title	Overall Survival (Phase II)
Time Frame	Up to 65 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	39
Median (Full Range) [months]	18.2

6. Secondary Outcome

Title	Progression-free Survival (Phase II)
Time Frame	Completion of study (up to 65 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	39
Median (Full Range) [months]	4.1

7. Secondary Outcome

Title	Frequency and Severity of Toxicities (Phase II)
Description	Treatment-related adverse events Grade ≥3 by NCI CTCAE 2.0.
Time Frame	Completion of study (up to 36 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	39
Neutropenia	14 82.4%
Febrile neutropenia	4 23.5%
Platelets	1 5.9%
Diarrhea	7 41.2%
Dehydration	2 11.8%
Fatigue	2 11.8%
Hypokalemia	1 5.9%
Hyponatremia	1 5.9%
Infection (without neutropenia)	1 5.9%
Myalgias	1 5.9%
Nausea	1 5.9%
Ocular	1 5.9%
Pain	1 5.9%
Stomatitis	1 5.9%

8. Secondary Outcome

Title	Prognostic Significance of Epithelial Growth Factor Receptor (EGFR) Expression
Time Frame	Completion of study (up to 36 months)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	0

9. Secondary Outcome

Title	Correlation of Baseline EGFR Levels With Clinical Outcome
Time Frame	Completion of study (up to 36 months)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	0

10. Secondary Outcome

Title	Correlation of Basal Levels of p27 With Response Rate and Overall Survival
Time Frame	Completion of study (up to 36 months)

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	0

11. Secondary Outcome

Title	Correlation of Phospho-EGFR With Increased p27 and Clinical Outcome
Time Frame	Completion of study

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	0

12. Secondary Outcome

Title	Correlation of EGFR Polymorphisms With Treatment Response and Clinical Outcome
Time Frame	Completion of study

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
Measure Participants	0

Adverse Events

Arm/Group Title	Phase I, Arm A (Completed)		Phase I, Arm B (Completed)		Phase II
Arm/Group Description	Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride once on days 2, 9, and 16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally		Patients receive docetaxel as in group I and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Patients may then continue to receive erlotinib hydrochloride alone in the absence of unacceptable toxicity or disease progression. docetaxel: Given IV erlotinib hydrochloride: Given orally		Patients receive docetaxel IV over 1 hour on day 1 and oral erlotinib hydrochloride at the MTD determined in group II of phase I once daily on days 2-16. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive erlotinib hydrochloride alone in the absence of disease progression or unacceptable toxicity. docetaxel: Given IV erlotinib hydrochloride: Given orally
All Cause Mortality
	Phase I, Arm A (Completed)		Phase I, Arm B (Completed)		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase I, Arm A (Completed)		Phase I, Arm B (Completed)		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/17 (11.8%)		5/25 (20%)		1/39 (2.6%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/17 (0%)		2/25 (8%)		0/39 (0%)
Neutropenia	0/17 (0%)		1/25 (4%)		1/39 (2.6%)
Leukocytes	0/17 (0%)		1/25 (4%)		0/39 (0%)
Hemoglobin	0/17 (0%)		1/25 (4%)		0/39 (0%)
Gastrointestinal disorders
GI Bleed	0/17 (0%)		1/25 (4%)		0/39 (0%)
Mucositis	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
General disorders
Fatigue	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Infections and infestations
Sepsis	1/17 (5.9%)		1/25 (4%)		0/39 (0%)
Clinically Documented Infection	1/17 (5.9%)		0/25 (0%)		0/39 (0%)
Metabolism and nutrition disorders
Anorexia	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/17 (5.9%)		0/25 (0%)		0/39 (0%)
Hypoxia	0/17 (0%)		1/25 (4%)		0/39 (0%)
Pulmonary Fibrosis	0/17 (0%)		1/25 (4%)		0/39 (0%)
Vascular disorders
Hypotension	1/17 (5.9%)		0/25 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Phase I, Arm A (Completed)		Phase I, Arm B (Completed)		Phase II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)		25/25 (100%)		38/39 (97.4%)
Blood and lymphatic system disorders
Neutropenia	10/17 (58.8%)		16/25 (64%)		14/39 (35.9%)
Febrile Neutropenia	3/17 (17.6%)		4/25 (16%)		4/39 (10.3%)
Hemoglobin	0/17 (0%)		1/25 (4%)		0/39 (0%)
Platelets	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Eye disorders
Ocular	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Gastrointestinal disorders
Diarrhea	0/17 (0%)		3/25 (12%)		7/39 (17.9%)
Nausea	1/17 (5.9%)		0/25 (0%)		1/39 (2.6%)
Stomatitis	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
General disorders
Fatigue	0/17 (0%)		1/25 (4%)		2/39 (5.1%)
Pain	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Infections and infestations
Infection (without neutropenia)	1/17 (5.9%)		3/25 (12%)		1/39 (2.6%)
Metabolism and nutrition disorders
Dehydration	0/17 (0%)		0/25 (0%)		2/39 (5.1%)
Hypokalemia	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Hyponatremia	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Musculoskeletal and connective tissue disorders
Myalgias	0/17 (0%)		0/25 (0%)		1/39 (2.6%)
Respiratory, thoracic and mediastinal disorders
Mucositis	0/17 (0%)		1/25 (4%)		0/39 (0%)
Skin and subcutaneous tissue disorders
Rash	0/17 (0%)		1/25 (4%)		0/39 (0%)

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.