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Trial record 1 of 1 for:    NCT01619423
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A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer (PLIANT)

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ClinicalTrials.gov Identifier: NCT01619423
Recruitment Status : Completed
First Posted : June 14, 2012
Results First Posted : July 6, 2018
Last Update Posted : July 6, 2018
Sponsor:
Collaborator:
Pharma Consulting Group AB
Information provided by (Responsible Party):
PledPharma AB

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Advanced Metastatic (Stage IV) Colorectal Cancer
Interventions Drug: PledOx (2 µmol/kg)
Drug: PledOx (5 µmol/kg)
Drug: PledOx (10 µmol/kg)
Drug: Placebo (0,9% NaCl)
Enrollment 186
Recruitment Details  
Pre-assignment Details 186 participants were enrolled and 186 started the study, however, two patients had too high basal manganese levels (detected after first treatment cycle) and were excluded from further treatment (screening failures) but are part of the safety population. 184 patients are part of the treatment population (11 in part 1 and 173 in part 2)
Arm/Group Title FOLFOX6 + 0,9% NaCl (Part 2a+2b) FOLFOX6 + PledOx 2 µmol/kg (Part 1, 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 1, 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 1, 2a)
Hide Arm/Group Description

Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Placebo (0,9% NaCl): Placebo (0,9% NaCl) is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (2 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (5 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (10 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

Period Title: Part 1 (Dose Escalation)
Started 0 5 3 5
Completed 0 3 3 5
Not Completed 0 2 0 0
Reason Not Completed
High basal Mn             0             2             0             0
Period Title: Part 2a
Started 15 13 0 11
Completed 15 13 0 11
Not Completed 0 0 0 0
Period Title: Part 2b
Started 45 44 45 0
Completed 45 44 45 0
Not Completed 0 0 0 0
Arm/Group Title FOLFOX6 + 0,9% NaCl (Part 2a+2b) FOLFOX6 + PledOx 2 µmol/kg (Part 1, 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 1, 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 1, 2a) Total
Hide Arm/Group Description

Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Placebo (0,9% NaCl): Placebo (0,9% NaCl) is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (2 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (5 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (10 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

Total of all reporting groups
Overall Number of Baseline Participants 60 62 48 16 186
Hide Baseline Analysis Population Description
Although no pre-specified Outcome Measures were performed on participants in Part 1, however, baseline data for all 186 participants is reported.
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 60 participants 62 participants 48 participants 16 participants 186 participants
62
(41 to 80)
63.5
(42 to 83)
62.6
(38 to 82)
61.3
(35 to 80)
62.6
(35 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 62 participants 48 participants 16 participants 186 participants
Female
46
  76.7%
46
  74.2%
26
  54.2%
7
  43.8%
125
  67.2%
Male
14
  23.3%
16
  25.8%
22
  45.8%
9
  56.3%
61
  32.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 62 participants 48 participants 16 participants 186 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
2
   4.2%
0
   0.0%
2
   1.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.7%
0
   0.0%
1
   2.1%
0
   0.0%
2
   1.1%
White
58
  96.7%
61
  98.4%
45
  93.8%
16
 100.0%
180
  96.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   1.7%
1
   1.6%
0
   0.0%
0
   0.0%
2
   1.1%
1.Primary Outcome
Title Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia)
Hide Description Percentage of patients, over cycle 1 to 8, with neuropathy grade 2 or higher (according to the Oxaliplatin Specific Sanofi Scale (OSSS) criteria related paraesthesiae/dysaesthesiae)
Time Frame Every second week during cycle 1-8, for up to 16 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo FOLFOX6 + PledOx 2 µmol/kg FOLFOX6 + PledOx 5+10 µmol/kg FOLFOX6 + PledOx 2+5+10 µmol/kg
Hide Arm/Group Description:
Control group

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (2 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Combined PledOx (5 and 10 µmol/kg groups): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Combined PledOx (2, 5 and 10 µmol/kg groups): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

Overall Number of Participants Analyzed 60 57 56 113
Measure Type: Count of Participants
Unit of Measure: Participants
14
  23.3%
11
  19.3%
6
  10.7%
17
  15.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, FOLFOX6 + PledOx 2 µmol/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.78
Confidence Interval (1-Sided) 10%
1.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, FOLFOX6 + PledOx 5+10 µmol/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.15
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.55
Confidence Interval (1-Sided) 10%
1.16
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, FOLFOX6 + PledOx 2+5+10 µmol/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.62
Confidence Interval (1-Sided) 10%
1.14
Estimation Comments [Not Specified]
Time Frame 30 days after last treatment for newly occuring AE:s and until resolution for ongoing, up to 2 years from baseline
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title FOLFOX6 + 0,9% NaCl (Part 2a+2b) Part 1 (Dose Escalation) FOLFOX6 + PledOx 2 µmol/kg (Part 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 2a)
Hide Arm/Group Description

Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Placebo (0,9% NaCl): Placebo (0,9% NaCl) is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

Part 1 is an open dose-escalation part with the doses 2, 5 and 10 µmol/kg of PledOx with the active ingridient calmangafodipir

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (2 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (5 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

PledOx (10 µmol/kg): PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

All-Cause Mortality
FOLFOX6 + 0,9% NaCl (Part 2a+2b) Part 1 (Dose Escalation) FOLFOX6 + PledOx 2 µmol/kg (Part 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 2a)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/60 (3.33%)   0/13 (0.00%)   1/57 (1.75%)   1/45 (2.22%)   1/11 (9.09%) 
Show Serious Adverse Events Hide Serious Adverse Events
FOLFOX6 + 0,9% NaCl (Part 2a+2b) Part 1 (Dose Escalation) FOLFOX6 + PledOx 2 µmol/kg (Part 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 2a)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/60 (10.00%)   2/13 (15.38%)   7/57 (12.28%)   3/45 (6.67%)   2/11 (18.18%) 
Blood and lymphatic system disorders           
Neutropenia   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Febrile neutropenia   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders           
Diarrhea   1/60 (1.67%)  0/13 (0.00%)  1/57 (1.75%)  1/45 (2.22%)  0/11 (0.00%) 
Ileus   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  1/11 (9.09%) 
Intestinal perforation   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Small intestine obstruction   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Subileus   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Nausea   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Constipation   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
General disorders           
Death   0/60 (0.00%)  0/13 (0.00%)  0/57 (0.00%)  1/45 (2.22%)  0/11 (0.00%) 
Cheast pain   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Pyrexia   1/60 (1.67%)  0/13 (0.00%)  1/57 (1.75%)  1/45 (2.22%)  0/11 (0.00%) 
Immune system disorders           
Hypersensitivty   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  1/11 (9.09%) 
Infections and infestations           
Device related infection   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Infection   0/60 (0.00%)  0/13 (0.00%)  0/57 (0.00%)  1/45 (2.22%)  1/11 (9.09%) 
Staphyloccocal infection   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Streptococcal sepsis   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications           
Humerus fracture   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Stoma site hemorrhage   0/60 (0.00%)  0/13 (0.00%)  1/57 (1.75%)  0/45 (0.00%)  0/11 (0.00%) 
Brain contusion   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Surgical and medical procedures           
Central venous catherization   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Stoma closure   1/60 (1.67%)  0/13 (0.00%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
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%
FOLFOX6 + 0,9% NaCl (Part 2a+2b) Part 1 (Dose Escalation) FOLFOX6 + PledOx 2 µmol/kg (Part 2a+2b) FOLFOX6 + PledOx 5 µmol/kg (Part 2b) FOLFOX6 + PledOx 10 µmol/kg (Part 2a)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   49/60 (81.67%)   10/13 (76.92%)   45/57 (78.95%)   35/45 (77.78%)   9/11 (81.82%) 
Blood and lymphatic system disorders           
Blood and lymphatic system disorder   49/60 (81.67%)  10/13 (76.92%)  45/57 (78.95%)  35/45 (77.78%)  9/11 (81.82%) 
Gastrointestinal disorders           
Gastrointestinal disorder   36/60 (60.00%)  9/13 (69.23%)  31/57 (54.39%)  32/45 (71.11%)  8/11 (72.73%) 
General disorders           
General disorders   35/60 (58.33%)  2/13 (15.38%)  24/57 (42.11%)  28/45 (62.22%)  2/11 (18.18%) 
Immune system disorders           
Type IV hypersensitivity reaction   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Infections and infestations           
Infections and infestations   4/60 (6.67%)  2/13 (15.38%)  6/57 (10.53%)  3/45 (6.67%)  0/11 (0.00%) 
Injury, poisoning and procedural complications           
Fall   0/60 (0.00%)  1/13 (7.69%)  0/57 (0.00%)  0/45 (0.00%)  0/11 (0.00%) 
Investigations           
Investigations   6/60 (10.00%)  1/13 (7.69%)  5/57 (8.77%)  5/45 (11.11%)  2/11 (18.18%) 
Metabolism and nutrition disorders           
Metabolism and nutrition disorders   19/60 (31.67%)  5/13 (38.46%)  18/57 (31.58%)  11/45 (24.44%)  2/11 (18.18%) 
Musculoskeletal and connective tissue disorders           
Musculosceletal and connective tissue   7/60 (11.67%)  2/13 (15.38%)  3/57 (5.26%)  6/45 (13.33%)  1/11 (9.09%) 
Nervous system disorders           
Nervous system disorder   47/60 (78.33%)  7/13 (53.85%)  44/57 (77.19%)  32/45 (71.11%)  8/11 (72.73%) 
Respiratory, thoracic and mediastinal disorders           
Respiratory, thoracic and mediastinal   7/60 (11.67%)  2/13 (15.38%)  7/57 (12.28%)  7/45 (15.56%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders           
Skin and subcutaneous tissue   7/60 (11.67%)  2/13 (15.38%)  7/57 (12.28%)  3/45 (6.67%)  2/11 (18.18%) 
Indicates events were collected by systematic assessment
The pre-specified statistical analysis plan (SAP) states; if the primary outcome meassure failed, then all additional outcome measures are considered exploratory. A selected number of the exploratory outcomes are presented in the linked publication
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Stefan Carlsson, MD, PhD, Chief Medical Officer
Organization: PledPharma AB
Phone: +46 8 679 72 10
Responsible Party: PledPharma AB
ClinicalTrials.gov Identifier: NCT01619423     History of Changes
Other Study ID Numbers: PP095, (PLIANT)
2012-001367-76 ( EudraCT Number )
First Submitted: May 25, 2012
First Posted: June 14, 2012
Results First Submitted: December 15, 2017
Results First Posted: July 6, 2018
Last Update Posted: July 6, 2018