CompletedNCT00390429Updated Dec 6, 2018Results posted

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

A Phase 1/2 interventional study of docetaxel and erlotinib hydrochloride in Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, sponsored by University of California, Davis. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-12-06.

Sponsored by University of California, Davis · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 81
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study 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)

Read the 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.

Conditions studied

Lung Cancer
Unspecified Adult Solid Tumor, Protocol Specific

Browse trials for

Lung Neoplasms 7,243

Keywords

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

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 81 is above the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

University of California, Davis is the lead sponsor of 798 studies on the registry; 146 are open to participants now.

Of its 65 completed or terminated interventional studies of FDA-regulated products, 43 (66%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: 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

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 81 participants (actual)

Study arms

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 · Drug: erlotinib hydrochloride
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 · Drug: erlotinib hydrochloride
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 · Drug: erlotinib hydrochloride

Interventions

Drugdocetaxel
Given IV
Also known as: Taxotere
Drugerlotinib hydrochloride
Given orally
Also known as: OSI-774, Tarceva

What researchers measure

Primary outcomes

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
Response Rate (Phase II)
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

Secondary outcomes

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
Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
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
Overall Survival (Phase II)
Time frame: Up to 65 months
Progression-free Survival (Phase II)
Time frame: Completion of study (up to 65 months)
Frequency and Severity of Toxicities (Phase II)
Treatment-related adverse events Grade ≥3 by NCI CTCAE 2.0.
Time frame: Completion of study (up to 36 months)
Prognostic Significance of Epithelial Growth Factor Receptor (EGFR) Expression
Time frame: Completion of study (up to 36 months)
Correlation of Baseline EGFR Levels With Clinical Outcome
Time frame: Completion of study (up to 36 months)
Correlation of Basal Levels of p27 With Response Rate and Overall Survival
Time frame: Completion of study (up to 36 months)
Correlation of Phospho-EGFR With Increased p27 and Clinical Outcome
Time frame: Completion of study
Correlation of EGFR Polymorphisms With Treatment Response and Clinical Outcome
Time frame: Completion of study

Results

Posted Oct 26, 2017

Participant flow

Participant flow — Overall Study
Milestone	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
Started	5	12	25	39
Completed	5	12	25	39
Not completed	0	0	0	0

Outcome measures

PrimarySafety 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
Reported as:: Count of participants · Participants

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])
Participants	Phase I, Arm A (Completed)	Phase I, Arm B (Completed)	Phase II
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])	17	25	39

PrimaryResponse Rate (Phase II)

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
Reported as:: Count of participants · Participants

Response Rate (Phase II)
Participants	Phase II
Response Rate (Phase II)	11

SecondaryComparison 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
Reported as:: Number · participants

Comparison of Toxicity of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
participants	Phase I, Group A (Completed)	Phase I, Group B (Completed)
Neutropenia	10	16
Febrile neutropenia	3	4
Hemoglobin	0	1
Diarrhea	0	3
Fatigue	0	1
Infection (without neutropenia)	1	3
Mucositis	0	1
Nausea	1	0
Rash	0	1

SecondaryMaximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])

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
Reported as:: Number · mg

Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
mg	Phase I, Group A (Completed)	Phase I, Group B (Completed)
Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])	600	200

SecondaryOverall Survival (Phase II)

Time frame:: Up to 65 months
Reported as:: Median · months

Overall Survival (Phase II)
months	Phase II
Overall Survival (Phase II)	18.2 (0 to 65)

SecondaryProgression-free Survival (Phase II)

Time frame:: Completion of study (up to 65 months)
Reported as:: Median · months

Progression-free Survival (Phase II)
months	Phase II
Progression-free Survival (Phase II)	4.1 (0 to 65)

SecondaryFrequency and Severity of Toxicities (Phase II)

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

Time frame:: Completion of study (up to 36 months)
Reported as:: Number · participants

Frequency and Severity of Toxicities (Phase II)
participants	Phase II
Neutropenia	14
Febrile neutropenia	4
Platelets	1
Diarrhea	7
Dehydration	2
Fatigue	2
Hypokalemia	1
Hyponatremia	1
Infection (without neutropenia)	1
Myalgias	1
Nausea	1
Ocular	1
Pain	1
Stomatitis	1

SecondaryPrognostic Significance of Epithelial Growth Factor Receptor (EGFR) Expression

Time frame:: Completion of study (up to 36 months)