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

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

— ARCHER 1042  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01465802
• Other study ID #: A7471042
• Status: Completed
• Phase: Phase 2
• Start date: December 26, 2011
• Est. completion date: May 18, 2015

Study information

• Verified date: December 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 236
• Est. completion date: May 18, 2015
• Est. primary completion date: May 18, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Dacomitinib
Dacomitinib 45 mg orally daily on a continuous schedule until disease progression, toxicity, death or withdrawal of consent
• Dacomitinib
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
• Doxycycline
Doxycycline or Doxycycline placebo BID for 4 weeks
• Probiotic
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 cream
Topical alclometasone diproprionate cream 0.05% applied to face, hands, feet, neck, back and chest at bedtime for 4 weeks

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Legacy Pharma Research	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St Alexius Medical Center	Bismarck	North Dakota
United States	Mercy Clinic Cancer & Hematology-Branson	Branson	Missouri
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore-Einstein Center for Cancer Care	Bronx	New York
United States	Josephine Ford Cancer Center-Downriver	Brownstown	Michigan
United States	'Fletcher Allen Health Care, Inc	Burlington	Vermont
United States	Office of Clinical Trials Research, Fletcher Allen Health Care, Inc.	Burlington	Vermont
United States	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina
United States	Rush University Medical Center, Division of Hematology & Oncology	Chicago	Illinois
United States	Ships Drugs to: Emmanuel Semmes, RPh (or Ami Patel, Pharm D) University of Chicago	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	The West Clinic, PC	Corinth	Mississippi
United States	Henry Ford Medical Center - Fairlane	Dearborn	Michigan
United States	Kaiser Permanente Colorado - Franklin	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Michael and Dianne Bienes Comprehensive Cancer Center, Holy Cross Hospital	Fort Lauderdale	Florida
United States	Investigational Product Center (IPC)	Fort Worth	Texas
United States	Investigational Products Center (IPC)	Fort Worth	Texas
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	St. Mary's Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Carolina Oncology Specialists, PA	Hickory	North Carolina
United States	Memorial Cancer Institute	Hollywood	Florida
United States	UCLA Hematology Oncology	Irvine	California
United States	Swedish Cancer Institute - Issaquah	Issaquah	Washington
United States	UC San Diego Medical Center - La Jolla	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	UC San Diego Moores Cancer Center - Investigational Drug Services	La Jolla	California
United States	Kaiser Permanente Colorado - Rock Creek	Lafayette	Colorado
United States	Cancer Care of North Florida, PA	Lake City	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Kaiser Permanente Colorado - Lonetree	Lonetree	Colorado
United States	Drug Management Only: UCLA West Medical Pharmacy	Los Angeles	California
United States	Drug Management Only: UCLA West Medical Pharmacy	Los Angeles	California
United States	Drug Management Only: UCLA West Medical Pharmacy Attn: Steven L. Wong, Pharm.D.	Los Angeles	California
United States	Drug Managment Only: UCLA West Medical Pharmacy	Los Angeles	California
United States	Regulatory Management Only TRIO-US Central Administration	Los Angeles	California
United States	Regulatory Management Only: TRIO-US Central Administration	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	UCLA Hematology Oncology	Los Angeles	California
United States	Westwood Bowyer Clinic	Los Angeles	California
United States	The West Clinic, PC	Memphis	Tennessee
United States	The West Clinic, PC	Memphis	Tennessee
United States	Beth Israel Comprehensive Cancer Center	New York	New York
United States	Beth Israel Medical Center	New York	New York
United States	Columbia University Medical Center - The New York Presbyterian Hospital	New York	New York
United States	Henry Ford Medical Center - Columbus	Novi	Michigan
United States	UCLA/Pasadena HealthCare	Pasadena	California
United States	Memorial West Cancer Institute	Pembroke Pines	Florida
United States	Illinois CancerCare, P.C.	Peoria	Illinois
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	Coastal Integrative Cancer Care	San Luis Obispo	California
United States	Cancer Center of Santa Barbara with SANSUM Clinic	Santa Barbara	California
United States	SANSUM Clinic	Santa Barbara	California
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	UCLA Hematology Oncology	Santa Monica	California
United States	UCLA Santa Monica Medical Center & Orthopaedic Hospital	Santa Monica	California
United States	Summit Cancer Care, PC	Savannah	Georgia
United States	Summit Cancer Care,PC	Savannah	Georgia
United States	Swedish Cancer Institute	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	Cancer Center of Santa Barbara with SANSUM Clinic	Solvang	California
United States	City of Hope South Pasadena Cancer Center	South Pasadena	California
United States	The West Clinic, PC	Southaven	Mississippi
United States	Mercy Clinic Cancer and Hematology - Chub O-Reilly Cancer Center	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stony Brook University Medical Center-Cancer Center	Stony Brook	New York
United States	UCLA/Santa Clarita Valley Cancer Center	Valencia	California
United States	Henry Ford Hospital and Medical Center - West Bloomfield	West Bloomfield	Michigan
United States	UCLA Cancer Center	Westlake Village	California
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	First 8 Weeks of Treatment
Primary	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.	First 8 Weeks of Treatment
Primary	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.	First 8 Weeks of Treatment
Primary	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.	First 8 Weeks of Treatment
Primary	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.	Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Primary	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.	First 8 Weeks of Treatment
Primary	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.	First 8 Weeks of Treatment
Primary	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.	Cycles 1, 2, 3, 4, 5, and 6, EoT and Follow-up
Primary	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	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).
Primary	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	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).
Primary	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.	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	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).	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)
Secondary	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.	Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Secondary	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.	Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Secondary	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.	Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Secondary	Mean Apparent Clearance (CL/F) for Dacomitinib on Cycle 2 Day 1 for Cohort I	CL/F was calculated as dose/AUCtau.	Cycle 2 Day 1: pre-dose and at 2, 4, 6, and 24 hours post-dose
Secondary	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.	Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.
Secondary	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.	Cohorts I to III: Pre-dose on Day 1 of Cycle 3 to 10.

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