Advanced Non-Squamous Non-Small Cell Lung CancerPhase 2NCT01204307
Influence of Prior Chemotherapy on Clinical Benefit With Erlotinib in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With or Without EGFR Gene Mutation
A Phase 2 study testing Docetaxel/cisplatin and Pemetrexed/cisplatin in people with Advanced Non-Squamous Non-Small Cell Lung Cancer, run by Chang Gung Memorial Hospital at 4 sites in Taiwan.
Trial summary
To compare the differential influence of 1st line doublet chemotherapy containing Docetaxel versus Pemetrexed on clinical efficacy of Erlotinib as a second line therapy in patients with relapsed or progressed non-squamous NSCLC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Non-Squamous Non-Small Cell Lung Cancer
- What is being tested?
- Docetaxel/cisplatin and Pemetrexed/cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 101 participants
- Where
- 4 sitesTaiwan
- Study dates
- Jan 2010to Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients > 18 years, <75 years old
- Pathological confirmation of non-squamous NSCLC
- Clinical stage IIIB or IV
- Measurable tumor size by RECIST criteria
- ECOG <2
- Adequate hematological laboratory parameters
- Adequate hepatic, renal laboratory parameters
Who cannot join
- Un-specified NSCLC
- Prior therapy with any chemotherapy or EGFR TKI or monoclonal antibodies
- Any unstable systemic disease (active infection, hypertension, unstable angina, CHF, liver cirrhosis, end stage renal failure etc., )
- Nursing or pregnant mothers
- Untreated Brain metastasis
- ECOG>2
Trial locations and contacts
4 sites in 1 country.
Taiwan4 sites
Chang Gung Memorial Hospital, Kaohsiung Branch
Kaohsiung City
Chang Gung Memorial Hospital
Taipei, Taipei, 10507
McKay Memorial Hospital
Taipei
Shin Kong Wu Ho-Su Memorial Hospital
Taipei
About this study
Official title: A Phase III Study to Investigate the Differential Influence of Prior Chemotherapy on the Efficacy of Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (IIIB, IV) With or Without EGFR Gene Mutation
To compare the differential influence of 1st line doublet chemotherapy containing Docetaxel versus Pemetrexed on clinical efficacy of Erlotinib as a second line therapy in patients with relapsed or progressed non-squamous NSCLC.
Read the detailed description
The clinical management of advanced non-small cell lung cancer (NSCLC) remains challenging. Initial therapies for advanced NSCLC with platinum-based regimens have shown consistent overall response rates of 30% to 40% with progression-free intervals of 4-5 months and 1-year survival rates of 35% to 40% [1-3]. First line doublet chemotherapy commonly used in daily practice includes Gemcitabine, vinorelbine, paclitaxel and docetaxel those have proven efficacy with platinum against best supportive care, prolonging survival for approximately 3 months. Recently, pemetrexed, a multi-target antifolate agent, has been introduced into the 1st line doublet chemotherapy with platinum-based regimen to have similar efficacy and a better safety profile compared to docetaxel or gemcitabine [4]. Although those agents seem to have equivalent efficacy, tolerability tends to be a concern for docetoxel.
Myelosuppression with the standard docetaxel schedule of 75 mg/m2 administered once every 3 weeks is extremely frequent and severe; neutropenia occurs in 54% to 67% of patients and febrile neutropenia occurs in 1.8% to 8.0% of patients [5, 6]. Moreover, non-hematologic toxicities, such as grade 3-4 asthenia (12% to 18%), and nausea and vomiting (1% to 3.6%), are not uncommon [5, 6]. To increase tolerability of docetaxel, alternative schedules have been extensively studied. Accumulating evidence suggests that a weekly schedule of docetaxel (35 mg/m2) reduces severe and febrile neutropenia without decreasing antitumor activity [7-10]. Nevertheless, no significant differences were observed for anemia, thrombocytopenia, and non-hematologic toxicity [7]. For the same reason, a lower dose of docetaxel (60 mg/m2 every 3 weeks) has been recommended in Japan [11, 12]. However, recent large scale trials with such a dose of docetaxel still revealed high incidences of grade 3 and 4 neutropenia (up to 82.9%) [12-14]. Different schedules of low dose docetaxel have not been studied, nor has a comparison been made between low dose docetaxel and the less toxic agent, pemetrexed.
Currently, the investigators have been following a schedule of weekly low dose docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks; 60 mg/m2 accumulated dose for each cycle) at our hospital in an effort to achieve better tolerability (in press-chemotherapy 2010). The investigators therefore perform an exploratory study, by prospective analysis, to investigate the efficacy and toxicity of such a low dose docetaxel schedule compared to that of pemetrexed in patients with NSCLC who are chemotherapy naive.
Erlotinib, an orally-available epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI), significantly prolongs survival and produces significant symptom and quality-of-life benefits compared with best supportive care in unselected patients with relapsed non-small-cell lung cancer (NSCLC) [15, 16]. In a large, phase III, placebo-controlled study (BR.21), erlotinib produced a survival benefit across all patient sub-groups studied [15].
- Being tested
- Docetaxel/cisplatin, Pemetrexed/cisplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docetaxel/cisplatinDrug
Also called Taxotere- made by Sanofi-Aventis.
The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles.
Pemetrexed/cisplatinDrug
Also called Alimta- made by LiLy.
The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| docetaxel/cisplatin | Experimental | The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles. Receives: Drug: Docetaxel/cisplatin |
| Pemetrexed/cisplatin | Active comparator | The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation. Receives: Drug: Pemetrexed/cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin
Eligible patients will be randomized to receive 1st line chemotherapy with either Docetaxel (60mg/m2)/Cisplatin (75mg/m2) or Pemetrexed (500mg/m2)/Cisplatin (75mg/m2) for 4-6 cycles. Patients will be followed up without any maintenance treatment after 4-6 cycles of chemotherapy.
Once patients are found tumor relapse or in progression, all the patients will be prescribed Erlotinib 150 mg/day until disease progression, unacceptable toxicity or death. Patients will be followed up every 2-3 months for their responsive rate.
Measured: 2-3 months
Secondary outcomes (1)
Progression-free survival and overall survival after erlotinib treatment with 1st line Docetaxel/cisplatin or Pemetrexed/cisplatin.
Erlotinib 150 mg daily will be given to patients who are in progression after 1st line cisplatin-base doublet chemotherapy. Treatment will continue until documented disease progression, or patient refusal to continue. The progression-free survival encompasses the time from the start date of the Erlotinib treatment to documented progression, or death from any cause. The Overall survival from each arm of treatment is calculated from the start date of the treatment to death or to the last follow-up visit.
Measured: 12-24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2010 (estimated)
- Study startJan 2010
- Primary completionDec 2014
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Non-Squamous Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Taiwan Chest Disease Association
- Responsible party
- Principal investigator, Chung Fu-Tsai, Chang Gung Memorial Hospital
- Investigators
- Han-Pin Kuo, MD, PhD, Study director, Taiwan Chest Disease Association and Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01204307
- Sponsor's protocol ID
- 99-1896C
- Status last verified
- Sep 2010
- First submitted
- 16 Sep 2010
- Last updated
- 28 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Feng PH, Lee KY, Chang YL, Chan YF, Kuo LW, Lin TY, Chung FT, Kuo CS, Yu CT, Lin SM, Wang CH, Chou CL, Huang CD, Kuo HP. CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med. 2012 Nov 15;186(10):1025-36. doi: 10.1164/rccm.201204-0636OC. Epub 2012 Sep 6.
PubMed 22955317
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Study to Investigate the Differential Influence of Prior Chemotherapy on the Efficacy of Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (IIIB, IV) With or Without EGFR Gene Mutation
- ClinicalTrials.gov ID
- NCT01204307
- Acronym / sponsor ID
- 99-1896C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Collaborators
- Taiwan Chest Disease Association
- Study start
- Jan 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 17 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the differential influence of 1st line doublet chemotherapy containing Docetaxel versus Pemetrexed on clinical efficacy of Erlotinib as a second line therapy in patients with relapsed or progressed non-squamous NSCLC.
Detailed description
The clinical management of advanced non-small cell lung cancer (NSCLC) remains challenging. Initial therapies for advanced NSCLC with platinum-based regimens have shown consistent overall response rates of 30% to 40% with progression-free intervals of 4-5 months and 1-year survival rates of 35% to 40% [1-3]. First line doublet chemotherapy commonly used in daily practice includes Gemcitabine, vinorelbine, paclitaxel and docetaxel those have proven efficacy with platinum against best supportive care, prolonging survival for approximately 3 months. Recently, pemetrexed, a multi-target antifolate agent, has been introduced into the 1st line doublet chemotherapy with platinum-based regimen to have similar efficacy and a better safety profile compared to docetaxel or gemcitabine [4]. Although those agents seem to have equivalent efficacy, tolerability tends to be a concern for docetoxel.
Myelosuppression with the standard docetaxel schedule of 75 mg/m2 administered once every 3 weeks is extremely frequent and severe; neutropenia occurs in 54% to 67% of patients and febrile neutropenia occurs in 1.8% to 8.0% of patients [5, 6]. Moreover, non-hematologic toxicities, such as grade 3-4 asthenia (12% to 18%), and nausea and vomiting (1% to 3.6%), are not uncommon [5, 6]. To increase tolerability of docetaxel, alternative schedules have been extensively studied. Accumulating evidence suggests that a weekly schedule of docetaxel (35 mg/m2) reduces severe and febrile neutropenia without decreasing antitumor activity [7-10]. Nevertheless, no significant differences were observed for anemia, thrombocytopenia, and non-hematologic toxicity [7]. For the same reason, a lower dose of docetaxel (60 mg/m2 every 3 weeks) has been recommended in Japan [11, 12]. However, recent large scale trials with such a dose of docetaxel still revealed high incidences of grade 3 and 4 neutropenia (up to 82.9%) [12-14]. Different schedules of low dose docetaxel have not been studied, nor has a comparison been made between low dose docetaxel and the less toxic agent, pemetrexed.
Currently, the investigators have been following a schedule of weekly low dose docetaxel (30 mg/m2 on days 1 and 8 every 3 weeks; 60 mg/m2 accumulated dose for each cycle) at our hospital in an effort to achieve better tolerability (in press-chemotherapy 2010). The investigators therefore perform an exploratory study, by prospective analysis, to investigate the efficacy and toxicity of such a low dose docetaxel schedule compared to that of pemetrexed in patients with NSCLC who are chemotherapy naive.
Erlotinib, an orally-available epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI), significantly prolongs survival and produces significant symptom and quality-of-life benefits compared with best supportive care in unselected patients with relapsed non-small-cell lung cancer (NSCLC) [15, 16]. In a large, phase III, placebo-controlled study (BR.21), erlotinib produced a survival benefit across all patient sub-groups studied [15].
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| docetaxel/cisplatin | Experimental | Drug: Docetaxel/cisplatinThe treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles. |
| Pemetrexed/cisplatin | Active comparator | Drug: Pemetrexed/cisplatinThe patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients > 18 years, <75 years old
- Pathological confirmation of non-squamous NSCLC
- Clinical stage IIIB or IV
- Measurable tumor size by RECIST criteria
- ECOG <2
Key exclusion criteria (6 listed)
- Un-specified NSCLC
- Prior therapy with any chemotherapy or EGFR TKI or monoclonal antibodies
- Any unstable systemic disease (active infection, hypertension, unstable angina, CHF, liver cirrhosis, end stage renal failure etc., )
- Nursing or pregnant mothers
- Untreated Brain metastasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Docetaxel/cisplatinAlso: Taxotere- made by Sanofi-Aventis.The treatment schedule comprises a maximum of six 3-week treatment cycles consisting of weekly docetaxel (30 mg/m2) and cisplatin (37.5 mg/m2) for 2 consecutive weeks followed by a 1-week treatment-free period. The patients will be assessed after each cycle and a final assessment will be done after three and six cycles. | Drug | docetaxel/cisplatin |
| Pemetrexed/cisplatinAlso: Alimta- made by LiLy.The patients are given pemetrexed (500 mg/m2 as a 10-min intravenous infusion) and cisplatin (75 mg/m2) on day 1 every 21 days. Dexamethasone (4 mg) is administered twice daily on the day before, the day of, and the day after each dose of pemetrexed. Oral folic acid supplementation (1000 mg) is administered daily, beginning approximately 2 weeks prior to the first dose of pemetrexed and continues until 3 weeks after treatment discontinuation. A 1000 mg vitamin B12 injection is administered intramuscularly approximately 1-2 weeks before the first dose of pemetrexed and is repeated approximately every 9 weeks until 3 weeks after therapy discontinuation. | Drug | Pemetrexed/cisplatin |
Primary outcome
Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin
Time frame: 2-3 months
Eligible patients will be randomized to receive 1st line chemotherapy with either Docetaxel (60mg/m2)/Cisplatin (75mg/m2) or Pemetrexed (500mg/m2)/Cisplatin (75mg/m2) for 4-6 cycles. Patients will be followed up without any maintenance treatment after 4-6 cycles of chemotherapy. Once patients are found tumor relapse or in progression, all the patients will be prescribed Erlotinib 150 mg/day until disease progression, unacceptable toxicity or death. Patients will be followed up every 2-3 months for their responsive rate.
1 secondary outcome
Progression-free survival and overall survival after erlotinib treatment with 1st line Docetaxel/cisplatin or Pemetrexed/cisplatin.
Time frame: 12-24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2015.
- Derived from this study: PubMed 22955317Feng PH, Lee KY, Chang YL, Chan YF, Kuo LW, Lin TY, Chung FT, Kuo CS, Yu CT, Lin SM, Wang CH, Chou CL, Huang CD, Kuo HP. CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med. 2012 Nov 15;186(10):1025-36. doi: 10.1164/rccm.201204-0636OC. Epub 2012 Sep 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Han-Pin Kuo, MD, PhD study director
Taiwan Chest Disease Association and Chang Gung Memorial Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel/cisplatin and Pemetrexed/cisplatin in people with Advanced Non-Squamous Non-Small Cell Lung Cancer, run by Chang Gung Memorial Hospital at 4 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate to erlotinib with Docetaxel/cisplatin or Pemetrexed/cisplatin (time frame: 2-3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01204307, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2015.