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Trial record 6 of 60 for:    TAS-102

A Phase I/II Study for the Safety and Efficacy of Panitumumab in Combination With TAS-102 for Patients With Colorectal Cancer (APOLLON)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02613221
Recruitment Status : Completed
First Posted : November 24, 2015
Results First Posted : June 24, 2019
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Intervention Drug: Panitumumab + TAS-102
Enrollment 56
Recruitment Details Participants took part in the study at 25 investigative sites in Japan, from 08 December 2015 to 30 March 2018.
Pre-assignment Details Participants with a historical diagnosis of RAS wild-type, unresectable, advanced/recurrent colorectal cancer were enrolled in this study.
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Period Title: Overall Study
Started 56
Safety Population: Received Study Drug 55
Completed 1
Not Completed 55
Reason Not Completed
Lack of efficacy (exacerbation)             50
Adverse Event             2
Voluntary Discontinuation             1
Delayed Treatment             1
Enrolled but Not Treated             1
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Baseline Participants 55
Hide Baseline Analysis Population Description
Safety Analysis Set, The safety analysis set was defined as all participants who received at least one dose of the study drug during the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants
59.5  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Female
26
  47.3%
Male
29
  52.7%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 55 participants
55
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 55 participants
162.5  (9.2)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 55 participants
62.66  (14.67)
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 55 participants
23.57  (4.39)
[1]
Measure Description: Body Mass Index = weight (kg)/[height (m)^2]
Duration of First-line Treatment   [1] 
Median (Full Range)
Unit of measure:  Days
Number Analyzed 55 participants
595.5
(72 to 2240)
[1]
Measure Description: Reported data were mean duration between the date of initiation of first-line treatment and the date of enrollment of this study.
Primary Tumor Location (Single/Multiple)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Single
54
  98.2%
Multiple
1
   1.8%
[1]
Measure Description: Reported data were number of participants with primary tumor location categorized by Single or Multiple at the start of this study.
Primary Tumor Location (Colon/Rectal)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Colon
34
  61.8%
Rectal
21
  38.2%
[1]
Measure Description: Reported data were number of participants with primary tumor location categorized by Colon or Rectal at the start of this study.
Primary Tumor Location (Right side/Left side)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Right side
7
  12.7%
Left side
48
  87.3%
[1]
Measure Description: Reported data were number of participants with primary tumor location categorized by Right side or Left side at the start of this study.
Number of metastatic organ  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
1
23
  41.8%
=>2
32
  58.2%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
0
38
  69.1%
1
17
  30.9%
[1]
Measure Description: ECOG-PS is measured on 6-point scale to assess participant's performance status. 0=Fully active (best), able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; 2=Ambulatory (>50% of waking hours), capable of all selfcare, but unable to carry out any work activities; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; 5=Dead (worst).
Resection of Primary Tumor   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Yes
43
  78.2%
No
12
  21.8%
[1]
Measure Description: Reported data were the number of participants who experienced resection of primary tumor. Yes; Had experienced, No; Had not experienced.
Adjuvant Chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Yes
16
  29.1%
No
39
  70.9%
[1]
Measure Description: Reported data were the number of participants who experienced adjuvant chemotherapy. Yes; Had experienced, No; Had not experienced.
Number of prior lines of chemotherapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
1
6
  10.9%
2
37
  67.3%
3
12
  21.8%
[1]
Measure Description: Reported data were the number of participants who experienced 1, 2, or 3 prior lines of chemotherapy before the start of this study.
Complication   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Had No Presence of Complications
10
  18.2%
Had Presence of Complications
45
  81.8%
[1]
Measure Description: Complications defined as a disease or a health condition for each participant at the start of study. Complications were classified as congenital anomalies, endocrine disorders, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, gastrointestinal (GI) disorders, renal disease and other complications. Other complications included all complications except for those mentioned above.
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicity (DLT) With Panitumumab Plus TAS-102 Combination Therapy
Hide Description DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia for more than 7 days under maximum supportive therapy; 2. Febrile neutropenia; 3. Platelet counts decreased of Grade 3 requiring platelet transfusion or blood platelet decreased of Grade 4; 4. If Course 2 was not initiated within 14 days due to AE related to the protocol treatment; 5. Grade 3 or higher non-hematologic toxicity that was considered clinically significant, except the following cases, Grade 3 gastrointestinal symptoms that could be controlled with supportive therapy (eg, appropriate use of antiemetics, antidiarrheals), and Grade 3 or higher electrolyte abnormalities that were not deemed clinically significant.
Time Frame Up to approximately 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
DLT Evaluation Set; DLT Evaluation Set was defined as participants who were enrolled and received at least one dose of the study drug in order to assess recommended dose of panitumumab in combination with TAS-102 (Total number of DLT Evaluation Set was 6).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Primary Outcome
Title Progression Free Survival (PFS) Rate at 6 Months
Hide Description PFS rate at 6 months was defined as the crude rate of surviving participants who survived or were not determined as progressive at 6 months from the day of enrollment. Although the subjects who had no imaging data on progression at 6 months after enrollment or the subjects who had lost to follow-up were included in the denominator, these subjects were not handled as progression-free. Progression included both progression disease (PD) based on diagnostic imaging assessed according to response evaluation criteria in solid tumors (RECIST) ver 1.1 and primary disease progression that cannot be confirmed by diagnostic imaging (clinical progression). PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
33.3
(22.77 to 45.32)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the period from the day of enrollment until death by all causes.
Time Frame From date of enrollment until the death, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Median (95% Confidence Interval)
Unit of Measure: Months
14.1
(12.18 to 19.29)
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the period from the day of enrollment until the day of documented progression or the day of death due to all causes whichever comes earlier. Progression included both PD based on diagnostic imaging assessed according to response evaluation criteria in solid tumors (RECIST) ver 1.1 and primary disease progression that cannot be confirmed by diagnostic imaging (clinical progression). PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame From date of enrollment until the date of progression or death, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Median (95% Confidence Interval)
Unit of Measure: Months
5.8
(4.46 to 6.50)
5.Secondary Outcome
Title Response Rate (RR)
Hide Description RR was defined as the percentage of participants who had shown complete response (CR) or partial response (PR) as the best overall response in accordance with the RECIST 1.1 criteria. The best overall response was CR, followed by PR, stable disease (SD), progressive disease (PD), and not evaluable (NE). CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization., SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time Frame From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
37.0
(24.29 to 51.26)
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier.
Time Frame From date of CR or PR until the date of PD or death, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Median (95% Confidence Interval)
Unit of Measure: Months
4.1
(2.29 to 6.29)
7.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the percentage of participants who had shown CR, PR, or SD as the best overall response in accordance with the RECIST version 1.1 criteria.
Time Frame From date of enrollment until the end of follow-up period, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
81.5
(68.57 to 90.75)
8.Secondary Outcome
Title Time to Treatment Failure (TTF)
Hide Description TTF was defined as the time from the date of enrollment to the date of the decision to discontinue the protocol treatment, the date of documented progression during the protocol treatment, or the date of death from any cause, whichever had come earlier.
Time Frame From date of enrollment until the date of the protocol treatment discontinuation, progression or death, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS); FAS was defined as participants who were enrolled and received at least one dose of protocol treatment (the recommended dose confirmed in the phase I part).
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 54
Median (95% Confidence Interval)
Unit of Measure: Months
5.8
(4.29 to 6.21)
9.Secondary Outcome
Title Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
Hide Description Adverse events (AEs) were any unfavorable medical events encountered in a participant treated with a drug. They were not limited to the events with clear causal relationship with treatment with the concerned drug. Treatment-emergent adverse events (TEAEs) were defined as AEs that had occurred after the initiation of protocol treatment.
Time Frame From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy, assessed up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set, The safety analysis set was defined as all participants who received at least one dose of the study drug during the study.
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description:
Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
Overall Number of Participants Analyzed 55
Measure Type: Count of Participants
Unit of Measure: Participants
55
 100.0%
Time Frame From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy, assessed up to approximately 29 months
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
 
Arm/Group Title Panitumumab + TAS-102
Hide Arm/Group Description Panitumumab 6 mg/kg every 2 weeks, plus TAS-102 35 mg/m² given orally twice a day in 5 days followed by a 2-day rest period for 2-week cycle, and then a 14-day rest period (28 days per 1 course).
All-Cause Mortality
Panitumumab + TAS-102
Affected / at Risk (%)
Total   6/55 (10.91%) 
Show Serious Adverse Events Hide Serious Adverse Events
Panitumumab + TAS-102
Affected / at Risk (%)
Total   13/55 (23.64%) 
Blood and lymphatic system disorders   
Anaemia  1  1/55 (1.82%) 
Febrile neutropenia  1  5/55 (9.09%) 
Gastrointestinal disorders   
Vomiting  1  1/55 (1.82%) 
General disorders   
General physical health deterioration  1  1/55 (1.82%) 
Infections and infestations   
Pyelonephritis  1  1/55 (1.82%) 
Injury, poisoning and procedural complications   
Infusion related reaction  1  1/55 (1.82%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Colon cancer  1  3/55 (5.45%) 
Metastases to spine  1  1/55 (1.82%) 
Rectal cancer  1  1/55 (1.82%) 
Cancer pain  1  1/55 (1.82%) 
Nervous system disorders   
Transient ischaemic attack  1  1/55 (1.82%) 
Product Issues   
Device breakage  1  1/55 (1.82%) 
Reproductive system and breast disorders   
Female genital tract fistula  1  1/55 (1.82%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease  1  1/55 (1.82%) 
Pleural effusion  1  1/55 (1.82%) 
1
Term from vocabulary, MedDRA Ver. 21.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Panitumumab + TAS-102
Affected / at Risk (%)
Total   54/55 (98.18%) 
Blood and lymphatic system disorders   
Anaemia  1  9/55 (16.36%) 
Ear and labyrinth disorders   
Vertigo  1  3/55 (5.45%) 
Gastrointestinal disorders   
Abdominal pain  1  6/55 (10.91%) 
Diarrhoea  1  17/55 (30.91%) 
Nausea  1  23/55 (41.82%) 
Stomatitis  1  39/55 (70.91%) 
Vomiting  1  8/55 (14.55%) 
Constipation  1  4/55 (7.27%) 
General disorders   
Fatigue  1  27/55 (49.09%) 
Malaise  1  10/55 (18.18%) 
Pyrexia  1  9/55 (16.36%) 
Infections and infestations   
Paronychia  1  23/55 (41.82%) 
Investigations   
Blood bilirubin increased  1  4/55 (7.27%) 
Neutrophil count decreased  1  36/55 (65.45%) 
Platelet count decreased  1  13/55 (23.64%) 
White blood cell count decreased  1  7/55 (12.73%) 
Metabolism and nutrition disorders   
Hypomagnesaemia  1  12/55 (21.82%) 
Decreased appetite  1  30/55 (54.55%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  5/55 (9.09%) 
Nervous system disorders   
Dysgeusia  1  12/55 (21.82%) 
Peripheral sensory neuropathy  1  11/55 (20.00%) 
Renal and urinary disorders   
Proteinuria  1  3/55 (5.45%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  4/55 (7.27%) 
Dermatitis acneiform  1  34/55 (61.82%) 
Palmar-plantar erythrodysaesthesia syndrome  1  14/55 (25.45%) 
Dry skin  1  27/55 (49.09%) 
Pruritus  1  9/55 (16.36%) 
Rash  1  11/55 (20.00%) 
1
Term from vocabulary, MedDRA Ver. 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02613221     History of Changes
Other Study ID Numbers: Panitumumab-1501
U1111-1176-3692 ( Other Identifier: WHO )
JapicCTI-153076 ( Registry Identifier: JapicCTI )
First Submitted: November 20, 2015
First Posted: November 24, 2015
Results First Submitted: October 4, 2018
Results First Posted: June 24, 2019
Last Update Posted: July 31, 2019