Non Small Cell Lung Cancer (NSCLC)Phase 2ARCHER 1042NCT01465802
Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO
A Phase 2 study testing Dacomitinib, Doxycycline and Probiotic in people with Non Small Cell Lung Cancer (NSCLC), run by Pfizer at 81 sites in 2 countries.
Trial summary
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer (NSCLC)
- What is being tested?
- Dacomitinib, Doxycycline and Probiotic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 236 participants
- Where
- 81 sitesin 2 countries
- Study dates
- 26 Dec 2011to 18 May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced Non-Small Cell Lung Cancer (NSCLC).
- For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated.
- For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed>12 months prior to enrollment.
- All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
- Estimated creatinine clearance ≥15 mL/min.
Who cannot join
- Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts).
- Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts).
- Patients with known diffuse interstitial lung disease (all cohorts).
- Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)
Trial locations and contacts
81 sites in 2 countries.
81 sites in 2 countries
United States79 sites
University Cancer & Blood Center, LLC
Athens, Georgia, 30607
Legacy Pharma Research
Bismarck, North Dakota, 58501
Mid Dakota Clinic, PC
Bismarck, North Dakota, 58501
St Alexius Medical Center
Bismarck, North Dakota, 58501
Mercy Clinic Cancer & Hematology-Branson
Branson, Missouri, 65616
Josephine Ford Cancer Center-Downriver
Brownstown, Michigan, 48183
'Fletcher Allen Health Care, Inc
Burlington, Vermont, 05401
Office of Clinical Trials Research, Fletcher Allen Health Care, Inc.
Burlington, Vermont, 05405
Charleston Hematology Oncology Associates, PA
Charleston, South Carolina, 29414
Rush University Medical Center, Division of Hematology & Oncology
Chicago, Illinois, 60612
Ships Drugs to: Emmanuel Semmes, RPh (or Ami Patel, Pharm D) University of Chicago
Chicago, Illinois, 60637
University of Chicago Medical Center
Chicago, Illinois, 60637
The West Clinic, PC
Corinth, Mississippi, 38834
Henry Ford Medical Center - Fairlane
Dearborn, Michigan, 48126
Kaiser Permanente Colorado - Franklin
Denver, Colorado, 80205
Henry Ford Hospital
Detroit, Michigan, 48202
City of Hope
Duarte, California, 91010
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Michael and Dianne Bienes Comprehensive Cancer Center, Holy Cross Hospital
Fort Lauderdale, Florida, 33308
Investigational Product Center (IPC)
Fort Worth, Texas, 76177
Investigational Products Center (IPC)
Fort Worth, Texas, 76177
St. Jude Heritage Healthcare
Fullerton, California, 92835
St. Mary's Hospital Regional Cancer Center
Grand Junction, Colorado, 81501
Carolina Oncology Specialists, PA
Hickory, North Carolina, 28602
Memorial Cancer Institute
Hollywood, Florida, 33021
UCLA Hematology Oncology
Irvine, California, 92604
Swedish Cancer Institute - Issaquah
Issaquah, Washington, 98029
UC San Diego Medical Center - La Jolla
La Jolla, California, 92037
UC San Diego Moores Cancer Center - Investigational Drug Services
La Jolla, California, 92037
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Kaiser Permanente Colorado - Rock Creek
Lafayette, Colorado, 80026
Cancer Care of North Florida, PA
Lake City, Florida, 32024
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89128
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Saint Barnabas Medical Center
Livingston, New Jersey, 07039
Kaiser Permanente Colorado - Lonetree
Lonetree, Colorado, 80124
Drug Management Only: UCLA West Medical Pharmacy
Los Angeles, California, 90095-7349
Drug Management Only: UCLA West Medical Pharmacy Attn: Steven L. Wong, Pharm.D.
Los Angeles, California, 90095
Drug Management Only: UCLA West Medical Pharmacy
Los Angeles, California, 90095
Drug Managment Only: UCLA West Medical Pharmacy
Los Angeles, California, 90095
Regulatory Management Only TRIO-US Central Administration
Los Angeles, California, 90095
Regulatory Management Only: TRIO-US Central Administration
Los Angeles, California, 90095
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
UCLA Hematology Oncology
Los Angeles, California, 90095
Westwood Bowyer Clinic
Los Angeles, California, 90095
The West Clinic, PC
Memphis, Tennessee, 38104
The West Clinic, PC
Memphis, Tennessee, 38120
Beth Israel Medical Center
New York, New York, 10003
Beth Israel Comprehensive Cancer Center
New York, New York, 10011
Columbia University Medical Center - The New York Presbyterian Hospital
New York, New York, 10032
Henry Ford Medical Center - Columbus
Novi, Michigan, 48377
UCLA/Pasadena HealthCare
Pasadena, California, 91105
Memorial West Cancer Institute
Pembroke Pines, Florida, 33028
Illinois CancerCare, P.C.
Peoria, Illinois, 61615
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103
Coastal Integrative Cancer Care
San Luis Obispo, California, 93401
SANSUM Clinic
Santa Barbara, California, 93105
Cancer Center of Santa Barbara with SANSUM Clinic
Santa Barbara, California, 93150
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454
UCLA Hematology Oncology
Santa Monica, California, 90404
UCLA Santa Monica Medical Center & Orthopaedic Hospital
Santa Monica, California, 90404
Summit Cancer Care,PC
Savannah, Georgia, 31404
Summit Cancer Care, PC
Savannah, Georgia, 31405
Swedish Cancer Institute
Seattle, Washington, 98104
Swedish Medical Center
Seattle, Washington, 98122
Cancer Center of Santa Barbara with SANSUM Clinic
Solvang, California, 93463
City of Hope South Pasadena Cancer Center
South Pasadena, California, 91030
The West Clinic, PC
Southaven, Mississippi, 38671
Mercy Hospital Springfield
Springfield, Missouri, 65804
Mercy Clinic Cancer and Hematology - Chub O-Reilly Cancer Center
Springfield, Missouri, 65807
Stony Brook University Medical Center-Cancer Center
Stony Brook, New York, 11794-9447
Montefiore-Einstein Center for Cancer Care
The Bronx, New York, 10461
Montefiore Medical Center
The Bronx, New York, 10467
UCLA/Santa Clarita Valley Cancer Center
Valencia, California, 91355
Henry Ford Hospital and Medical Center - West Bloomfield
West Bloomfield, Michigan, 48322
UCLA Cancer Center
Westlake Village, California, 91361
Cancer Center of Kansas
Wichita, Kansas, 67208
Cancer Center of Kansas
Wichita, Kansas, 67214
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
South Korea2 sites
Seoul National University Hospital
Seoul, 110-744
Severance Hospital, Yonsei University Health System
Seoul, 120-752
About this study
Official title: ARCHER 1042: A PHASE 2 STUDY OF DACOMITINIB IN ADVANCED NON-SMALL CELL LUNG CANCER (POST-CHEMOTHERAPY OR SELECT FIRST LINE PATIENTS) TO EVALUATE PROPHYLACTIC INTERVENTION ON DERMATOLOGIC AND GASTROINTESTINAL ADVERSE EVENTS AND PATIENT REPORTED OUTCOMES
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).
- Conditions
- Non Small Cell Lung Cancer (NSCLC)
- Being tested
- Dacomitinib, Doxycycline, Probiotic, Alclometasone cream
- Keywords
- non-small cell lung cancer, advanced, previously treated
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DacomitinibDrug
Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
DacomitinibDrug
Dacomitinib 45 mg orally daily on a continuous schedule for the first 10 days in Cycle 1, followed by 4 days off treatment, followed by continuous daily dosing until disease progression, toxicity, death or withdrawal of consent
DoxycyclineDrug
Doxycycline or Doxycycline placebo BID for 4 weeks
ProbioticDrug
VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28)
Alclometasone creamDrug
Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Cohort I | Experimental | Arm A: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline placebo orally BID for 4 weeks Arm B: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline 100 mg orally BID for 4 weeks Receives: Drug: Dacomitinib; Drug: Doxycycline |
| Cohort II | Experimental | Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28) Receives: Drug: Dacomitinib; Drug: Probiotic; Drug: Alclometasone cream |
| Cohort III | Experimental | Cohort III is an interrupted dosing schedule of dacomitinib in the first cycle only Receives: Drug: Dacomitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
SDAEI of all causality and all grades were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.
95% confidence interval (CI) calculated using exact method based on binomial distribution.
After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 1 was not conducted in Cohort I Arm C.
Measured: First 8 Weeks of Treatment
Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. Adverse events (AEs) were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 4.0).
95% CI calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 2 was not conducted in Cohort I Arm C.
Measured: First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I
Patient Reported Outcomes (PROs) of Health Related Quality of Life (HRQoL) \& disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if greater than (>) 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.
Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
Measured: First 8 Weeks of Treatment
Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Diarrhea AEs of all causality, all grade and Grade ≥2 were evaluated in participants in Cohort II. AEs were graded for severity using the NCI-CTCAE, Version 4.0.
95% CI calculated using exact method based on binomial distribution.
Measured: First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II
Diarrhea severity was assessed using the modified-OMDQ. This questionnaire is comprised of 6 questions in total; however, only two items relate to diarrhea symptoms (item 5 and item 6). Symptoms scores were developed for both the full questionnaire and for the diarrhea-only questions for each completed survey. Mucositis questions were transformed to a score range of 0 to 10. Increasing OMDQ values are associated with greater symptom burden.
Modified OMDQ completion criteria were defined as completion of all 4 questions (questions 2, 4, 5 and 6).
M/T = mouth and throat.
Measured: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II
SDAEI of all causality and all grades were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer.
95% CI calculated using exact method based on binomial distribution.
Measured: First 8 Weeks of Treatment
Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. AEs were graded for severity using the NCI-CTCAE, Version 4.0.
95% CI calculated using exact method based on binomial distribution.
Measured: First 8 Weeks of Treatment
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II
PROs of HRQoL and disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if > 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant.
Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
Measured: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
AUC0-24 is the area under the plasma concentration-time curve (AUC) from time 0 to 24 hours post-dose. AUC0-120 is the AUC from time 0 to 120 hours post-dose. AUC was calculated by the linear trapezoidal method using a non-compartmental pharmacokinetic (PK) analysis.
ng*hr/mL = nanogram hours per milliliter
Measured: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter
Measured: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
Measured: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Secondary outcomes (7)
Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III
Medications used concomitantly for SDAEIs, diarrhea and mucositis were evaluated for all participants who received dacomitinib on a continuous basis with a preemptive prophylactic (Cohorts I and II) or as an interrupted dosing regimen (Cohort III).
Measured: Screening to the Post-Teatment Follow-Up Visit (at least 28 days and no more than 35 days after the end of dacomitinib treatment due to progression of disease, intolerance to dacomitinib treatment, or participant withdrawal)
Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
AUCtau was the AUC from time 0 to the end of the dosing interval, where the dosing interval was 24 hours. AUCtau was calculated by the linear/log trapezoidal method using a non-compartmental PK analysis.
Measured: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Cmax was obtained from direct inspection of the data.
Measured: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
Measured: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I
CL/F was calculated as dose/AUCtau.
Measured: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III
Ctrough was the pre-dose plasma concentration of dacomitinib at steady state obtained from direct inspection of the data.
Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.
Measured: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III
Ctrough was the pre-dose plasma concentration of the dacomitinib metabolite PF-05199265 at steady state obtained from direct inspection of the data.
Number of participants analyzed is the total number of participants in the treatment group in the indicated population, n is the number of participants contributing to the summary statistics.
Measured: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study start26 Dec 2011
- Primary completion18 May 2015
- Study completion18 May 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by PfizerThe 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
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01465802
- Sponsor's protocol ID
- A7471042
- Acronym
- ARCHER 1042
- Status last verified
- Dec 2018
- First submitted
- 20 Oct 2011
- Last updated
- 9 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ARCHER 1042: A PHASE 2 STUDY OF DACOMITINIB IN ADVANCED NON-SMALL CELL LUNG CANCER (POST-CHEMOTHERAPY OR SELECT FIRST LINE PATIENTS) TO EVALUATE PROPHYLACTIC INTERVENTION ON DERMATOLOGIC AND GASTROINTESTINAL ADVERSE EVENTS AND PATIENT REPORTED OUTCOMES
- ClinicalTrials.gov ID
- NCT01465802
- Acronym / sponsor ID
- ARCHER 1042 / A7471042
- Conditions
- Non Small Cell Lung Cancer (NSCLC)
- Keywords
- non-small cell lung cancer, advanced, previously treated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 236 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 26 Dec 2011 (actual)
- Primary completion
- 18 May 2015 (actual)
- Study completion
- 18 May 2015 (actual)
- First posted
- 7 Nov 2011 (estimated)
- Results
- Posted 17 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the impact of prophylactic treatment on the incidence of adverse events in advanced NSCLC patients (post chemotherapy) treated with dacomitinib daily as a single agent. To assess the impact of an interrupted dacomitinib dosing schedule in Cycle 1 on the incidence of adverse events in first-line advanced NSCLC patients with an EGFR mutation (HER-1 mutation, HER-2 mutation or HER-2 amplification).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort I | Experimental | Drug: Dacomitinib, Drug: DoxycyclineArm A: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline placebo orally BID for 4 weeks Arm B: Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Doxycycline 100 mg orally BID for 4 weeks |
| Cohort II | Experimental | Drug: Dacomitinib, Drug: Probiotic, Drug: Alclometasone creamDacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks VSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28) |
| Cohort III | Experimental | Drug: DacomitinibCohort III is an interrupted dosing schedule of dacomitinib in the first cycle only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Advanced Non-Small Cell Lung Cancer (NSCLC).
- For Cohort I and Cohort II, advanced NSCLC patients must have received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC and who have failed (ie, progressed or intolerant due to toxicity which precludes further treatment) standard therapy for advanced or metastatic disease. To be considered intolerant to treatment, a patient must have received at least two cycles to be considered previously treated.
- For Cohort III, advanced NSCLC patients must not have received prior systemic treatment for their advanced disease and require a known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification. Cohort III patients could have received prior adjuvant chemotherapy for Stage I-III disease or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed>12 months prior to enrollment.
- All cohorts, patients must have evidence of disease; however, measurable disease is not required to enroll.
- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
Key exclusion criteria (4 listed)
- Prior treatment with an EGFR-targeted or HER-targeted agent (all cohorts).
- Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments (all cohorts).
- Patients with known diffuse interstitial lung disease (all cohorts).
- Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II)
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 |
|---|---|---|
| DacomitinibDacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent | Drug | Cohort I, Cohort II |
| DacomitinibDacomitinib 45 mg orally daily on a continuous schedule for the first 10 days in Cycle 1, followed by 4 days off treatment, followed by continuous daily dosing until disease progression, toxicity, death or withdrawal of consent | Drug | Cohort III |
| DoxycyclineDoxycycline or Doxycycline placebo BID for 4 weeks | Drug | Cohort I |
| ProbioticVSL#3 probiotic 4 capsules orally daily or 1 sachet orally daily for up to 5 weeks (starting between Day minus 7 to Day minus 4 and continuing through Day 28) | Drug | Cohort II |
| Alclometasone creamTopical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks | Drug | Cohort II |
Primary outcome
Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
Time frame: First 8 Weeks of Treatment
SDAEI of all causality and all grades were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. 95% confidence interval (CI) calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 1 was not conducted in Cohort I Arm C.
Percentage of Participants With SDAEI (All Causality, Grade Greater Than or Equal to [≥] 2) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I
Time frame: First 8 Weeks of Treatment
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort I. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. Adverse events (AEs) were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 4.0). 95% CI calculated using exact method based on binomial distribution. After protocol amendment 1, Arm C was removed from Cohort I and enrollment to Arm C was terminated. Only 7 participants were enrolled in Cohort I Arm C as a result. Given the smaller sample size, analyse of Outcome Measure 2 was not conducted in Cohort I Arm C.
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) by Treatment Arm for Cohort I
Time frame: First 8 Weeks of Treatment
Patient Reported Outcomes (PROs) of Health Related Quality of Life (HRQoL) \& disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if greater than (>) 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant. Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
Percentage of Participants With Diarrhea AEs (All Causality, All Grade and Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Time frame: First 8 Weeks of Treatment
Diarrhea AEs of all causality, all grade and Grade ≥2 were evaluated in participants in Cohort II. AEs were graded for severity using the NCI-CTCAE, Version 4.0. 95% CI calculated using exact method based on binomial distribution.
Mean Change From Baseline (Cycle 1 Day 1) Modified Oral Mucositis Daily Questionnaire (OMDQ) Scores (Mouth and Throat Soreness Categories and Scale, and Diarrhea Categories and Scale) for Cohort II
Time frame: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Diarrhea severity was assessed using the modified-OMDQ. This questionnaire is comprised of 6 questions in total; however, only two items relate to diarrhea symptoms (item 5 and item 6). Symptoms scores were developed for both the full questionnaire and for the diarrhea-only questions for each completed survey. Mucositis questions were transformed to a score range of 0 to 10. Increasing OMDQ values are associated with greater symptom burden. Modified OMDQ completion criteria were defined as completion of all 4 questions (questions 2, 4, 5 and 6). M/T = mouth and throat.
Percentage of Participants With SDAEI (All Causality, All Grade) in the First 8 Weeks of Treatment for Cohort II
Time frame: First 8 Weeks of Treatment
SDAEI of all causality and all grades were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. 95% CI calculated using exact method based on binomial distribution.
Percentage of Participants With SDAEI (All Causality, Grade ≥2) in the First 8 Weeks of Treatment for Cohort II
Time frame: First 8 Weeks of Treatment
SDAEI of all causality and Grade ≥2 were evaluated in participants in Cohort II. These SDAEIs included dermatitis acneiform, dry skin, exfoliative rash, nail discoloration, nail disorder, paronychia, pruritus, rash, skin exfoliation, skin fissures, skin infection, skin laceration and skin ulcer. AEs were graded for severity using the NCI-CTCAE, Version 4.0. 95% CI calculated using exact method based on binomial distribution.
Mean Change From Baseline (Cycle 1 Day 1) Skindex-16 Scale Scores (Total Score, Symptoms Score, Emotion Score, and Functioning Score) for Cohort II
Time frame: Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
PROs of HRQoL and disease/treatment-related symptoms were assessed using Dermatologic Survey (Skindex-16) that assesses "bother". It includes 3 multi-item scales: symptoms, emotions \& functioning. Individual scaled scores \& total scores were determined. Skindex questions were transformed to a linear scale of 0 (never bothered) to 100 (always bothered). Subscale scores are an average of non-missing questions in a given scale if > 75% of total subscale questions are non-missing. The Total Score is an average of all non-missing questions in the Skindex if >75% of total questions are non-missing. A negative change score represents a better quality of life. A change score of 10 points is considered clinically significant. Skindex completion criteria were defined as completion of 3 out of 4 items for questions 1 to 4, 6 out of 7 items for questions 5 to 11, 4 out of 5 items for questions 12 to 16 for the visit.
Mean Area Under the Plasma Concentration Time Curve From 0 to 24 Hours (AUC0-24) and From 0 to 120 Hours (AUC0-120) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Time frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
AUC0-24 is the area under the plasma concentration-time curve (AUC) from time 0 to 24 hours post-dose. AUC0-120 is the AUC from time 0 to 120 hours post-dose. AUC was calculated by the linear trapezoidal method using a non-compartmental pharmacokinetic (PK) analysis. ng*hr/mL = nanogram hours per milliliter
Mean Maximum Observed Plasma Concentrations (Cmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Time frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Cmax was obtained from direct inspection of the data. ng/mL = nanograms per milliliter
Median Time of Occurrence of Cmax (Tmax) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 1 Days 10 to 15 for Cohort III
Time frame: Cycle 1 Day 10: Pre-dose and 2, 4, 6, 24, 48, 72, 96, and 120 hours post-dose (the 120 hour sample was obtained on Day 15 pre-dose).
Tmax was obtained from direct inspection of the data as the time of first occurence of Cmax.
7 secondary outcomes
Percentage of Participants Receiving Any Concomitant Drug or Non-Drug Treatment for SDAEI, Diarrhea and Mucositis for Cohort I by Treatment Arm, Cohort II, and Cohort III
Time frame: Screening to the Post-Teatment Follow-Up Visit (at least 28 days and no more than 35 days after the end of dacomitinib treatment due to progression of disease, intolerance to dacomitinib treatment, or participant withdrawal)
Mean AUC From 0 to the End of the Dosing Interval (AUC0-tau) for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Time frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Cmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Time frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Median Tmax for Dacomitinib and Its Metabolite PF-05199265 on Cycle 2 Day 1 for Cohort I
Time frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I
Time frame: Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Mean Plasma Trough Concentrations (Ctrough) for Dacomitinib by Visit for Cohorts I, II and III
Time frame: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Mean Plasma Ctrough for PF-05199265 by Visit for Cohorts I, II and III
Time frame: Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Results and safety
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Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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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.
Pfizer CT.gov Call Center study director
Pfizer
81 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dacomitinib, Doxycycline and Probiotic in people with Non Small Cell Lung Cancer (NSCLC), run by Pfizer at 81 sites in 2 countries.
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 6 inclusion and 4 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 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 81 sites in United States, South Korea. 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?
Yes. Results are posted in the registry (first posted 17 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Select Dermatologic Adverse Events of Interest (SDAEI) (All Causality, All Grade) in the First 8 Weeks of Treatment by Treatment Arm for Cohort I (time frame: First 8 Weeks of Treatment). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2019.