Non-small Cell Lung Cancer
Conditions
Keywords
non-small cell, lung cancer
Brief summary
This is a Phase 1/Phase 2 study of STI571 combined with docetaxel and cisplatin for treatment of patients with recurrent and metastatic Non-Small Cell Lung Cancer (NSCLC). This research study has 2 parts to it. The first part (Phase 1) is called a dose-escalation. Not all subjects enrolled into this phase of the study will receive the same dose. The purpose of the dose-escalation is to determine the highest safe dose of STI571 that can be used in combination with docetaxel and cisplatin. That dose will be used in Phase 2.
Interventions
DRUGDocetaxel, Cisplatin and STI571
Treatment will consist of docetaxel plus cisplatin IV every 21days and oral STI571 given on Days -5 to 2 with each chemotherapy cycle. A maximum of 6 cycles will be given. Phase 1 dose levels are: * Level 1 Docetaxel/Cisplatin 60 mg/m2, STI571 300mg * Level 2 Docetaxel/Cisplatin 60 mg/m2, STI571 400mg * Level 3 Docetaxel/Cisplatin 70 mg/m2, STI571 400mg * Level 4 Docetaxel/Cisplatin 70 mg/m2, STI571 600mg * Level 5 Docetaxel/Cisplatin 75 mg/m2, STI571 600mg * Level 6 Docetaxel/Cisplatin 75 mg/m2, STI571 800mg Once the MTD level has been established, the previous dose level will be the dosing schedule for Phase II.
DRUGDocetaxel
DRUGCisplatin
Sponsors
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytologically recurrent, or advanced NSCLC: Stage IV disease; or Stage IIIB due to malignant pleural effusion is allowed- only if successfully pleurodesed. * Tumor tissue slides must express phosophorylated pdgf-rB by IHC. * At least one measurable target lesion as defined by RECIST criteria that has not been irradiated. * No prior chemotherapy treatment for this disease will be allowed. Patients with brain metastasis will have to be, after appropriate treatment, neurologically stable for at least 1-2 weeks (off steroids) prior to study enrollment. * ECOG performance status 0-1. * Meets initial laboratory parameters. * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
Exclusion criteria
* Any prior treatment with a biologic response modifier or chemotherapeutic agent for this disease. * Any concomitant malignancy except non-melanoma skin cancer or in-situ carcinoma of the cervix. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to STI571 and/or docetaxel, or other drugs formulated with polysorbate 80 and/or cisplatin. * Patients with: * Contrast allergy. * GI bleed ≤ 1 month from study enrollment. * Intermittent or chronic oxygen requirements. * Pulse oximetry \<90%. * Grade 3 dyspnea. * History of poorly regulated anticoagulation with warfarin. * Edema or fluid retention grade \>1. * Neuropathy grade ≥1. * Uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, ≤3 months myocardial infarction or cardiac arrhythmia. * Psychiatric illness/social situations that would limit compliance with study requirement or that would prevent informed consent or psychiatric illness/social situations requiring inpatient treatment within the past 3 months. * Any type of hearing impairment. * Known HIV infection. * Receiving other investigational agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 - Maximum Tolerated Dose (MTD) of STI571 | After cycle 1, day 22 | To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin, when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. |
| Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin | After cycle 1, day 22 | To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. |
| Phase II - Radiographic Response | After Cycle 6, approximately 18 weeks. | The percentage of patients with a complete or partial response. Responses for the Phase II portion of the trial will be by Response Evaluation Criteria In Solid Tumors (RECIST) criteria as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: 1 Year Survival | 1 year | Phase II: Percentage of patients alive 1 year from the start of protocol treatment. |
| Change in Gd-MRI Measurement | Day 7 | The change in Gd-MRI perfusion/permeability measurement between pre and post 7-day of STI571 treatment. |
Participant flow
Recruitment details
Patients with Advanced Non-Small Cell Lung Cancer were enrolled from November 2004 to April 2009. The study was closed due to poor accrual.
Pre-assignment details
Overall, 72 subject signed a consent form and 43 went on to start treatment on study. Of the 24 subjects who signed a consent form for Phase 1, 9 were screen failures and did not start study treatment. Of the 48 subjects who signed a consent form for Phase 2, 20 were screen failures and did not start study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 Eligible subjects will be enrolled in the Phase I portion of the study to determine the MTD of STI571 in combination with docetaxel plus cisplatin, given every three weeks. STI will be given intermittently for 7 days (Day -5 to Day 2) When MTD is established, Phase II study will evaluate for combined modality safety, tolerability and efficacy (response rate vs. historical control). All subjects will start with STI571 therapy alone for 7 days; pre and post STI571 treatment (Days -8 and 0) | 15 |
| Phase 2 The objective of this two-stage Phase II study is to determine whether the combination of STI571, docetaxel, and cisplatin merits inclusion in a randomized study for chemotherapy-naïve patients with advanced NSCLC. The dose for the Phase 2 portion of the trial will be IV Docetaxel / Cisplatin 60 / 60 mg/m2 and 400 mg STI571 PO QD | 28 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1 | Phase 2 | Total |
|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 12.5 | 60.0 years STANDARD_DEVIATION 9.5 | 57.7 years STANDARD_DEVIATION 11.3 |
| Region of Enrollment United States | 15 participants | 28 participants | 43 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 16 Participants |
| Sex: Female, Male Male | 10 Participants | 17 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 15 | 26 / 28 |
| serious Total, serious adverse events | 9 / 15 | 15 / 28 |
Outcome results
Primary
Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin
To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC.
Time frame: After cycle 1, day 22
Population: One patient only received the lead-in dose of STI571 prior to withdrawing from the study without a DLT. This subject is not included in the DLT determination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1 | Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin | Docetaxel | 60 mg/m2 |
| Phase 1 | Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin | Cisplatin | 60 mg/m2 |
Primary
Phase 1 - Maximum Tolerated Dose (MTD) of STI571
To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin, when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC.
Time frame: After cycle 1, day 22
Population: One patient only received the lead-in dose of STI571 prior to withdrawing from the study without a DLT. This subject is not included in the DLT determination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Phase 1 - Maximum Tolerated Dose (MTD) of STI571 | 400 mg |
Primary
Phase II - Radiographic Response
The percentage of patients with a complete or partial response. Responses for the Phase II portion of the trial will be by Response Evaluation Criteria In Solid Tumors (RECIST) criteria as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Time frame: After Cycle 6, approximately 18 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Phase II - Radiographic Response | 25 percentage of participants |
Secondary
Change in Gd-MRI Measurement
The change in Gd-MRI perfusion/permeability measurement between pre and post 7-day of STI571 treatment.
Time frame: Day 7
Population: Because the study was terminated prior to completion, correlative studies were not run.
Secondary
Phase 2: 1 Year Survival
Phase II: Percentage of patients alive 1 year from the start of protocol treatment.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1 | Phase 2: 1 Year Survival | 61 percentage of participants |