Trial Outcomes & Findings for Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer (NCT NCT00655499)

Last Updated: 2021-09-21

Results Overview

Per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) for target lesions and radiogically assessed (CT Scans; optionally MRI): Complete Response (CR; Disappearance of all target lesions) or Partial Response (PR; At least a 30% decrease in the sum of the LD of target lesions) during the combination therapy phase.Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Up to 20 months

Results posted on

2021-09-21

Participant Flow

From July 2008 to Oct. 2010, 69 patients were enrolled in the study, 4 were not eligible.The study was conducted in 11 French centers

Patient wih pathologically confirmed mCRC, KRAS codon 12 and 13 wild type, previously treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab. Eligibility criteria also included : age ≥ 18 years, normal hematopoietic , hepatic and renal functions, measurable disease.No prior treatment with anti-EGFR antibodies.

Participant milestones

Participant milestones
Measure	Panitumumab Combined With Irinotecan 65 patients were eligible (69 patients were enrolled and 4 patients were not eligible).
Overall Study STARTED	69
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Panitumumab Combined With Irinotecan 65 patients were eligible (69 patients were enrolled and 4 patients were not eligible).
Overall Study not eligible	4

Baseline Characteristics

Panitumumab and Irinotecan as Third-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panitumumab Combined With Irinotecan n=65 Participants 1cycle every 14 days (J1=J15). Panitumumab : 6mg/kg in IV infusion over 60 minutes on day 1. Irinotecan : 180mg/m² in IV infusion over 90 minutes on day 1 just after panitumumab administration
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	31 Participants n=5 Participants
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants
Region of Enrollment France	65 participants n=5 Participants
ECOG Performance status ECOG performance status - PS = 0	25 participants n=5 Participants
ECOG Performance status ECOG - PS=1	33 participants n=5 Participants
ECOG Performance status ECOG - PS=2	7 participants n=5 Participants
Primary tumor type Colon	45 participants n=5 Participants
Primary tumor type Rectum	17 participants n=5 Participants
Primary tumor type Both	3 participants n=5 Participants
Number of metastatic sites 1 metastatic site	37 participants n=5 Participants
Number of metastatic sites >1 metastatic site	28 participants n=5 Participants
Adjuvant chemotherapy Yes	17 participants n=5 Participants
Adjuvant chemotherapy No	48 participants n=5 Participants
Time between diagnosis and inclusion < 12 months	13 participants n=5 Participants
Time between diagnosis and inclusion ≥12-24 months	21 participants n=5 Participants
Time between diagnosis and inclusion > 24 months	31 participants n=5 Participants
First line chemotherapy Oxaliplatin-based therapy	42 participants n=5 Participants
First line chemotherapy Irinotecan-based therapy	22 participants n=5 Participants
First line chemotherapy Oxaliplatin- and irinotecan-based therapy	1 participants n=5 Participants
Second line chemotherapy Oxaliplatin-based therapy	14 participants n=5 Participants
Second line chemotherapy Irinotecan-based therapy	43 participants n=5 Participants
Second line chemotherapy No second line	8 participants n=5 Participants
Prior treatment with bevacizumab No	12 participants n=5 Participants
Prior treatment with bevacizumab Yes	53 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 20 months

Population: Panitumumab combined with irinotecan

Outcome measures

Outcome measures
Measure	Panitumumab Combined With Irinotecan n=65 Participants 69 patients were enrolled in the study. 4 patients were not eligible. 65 eligible patients were analysed
Objective Response Rate (ORR) During the Combination Therapy Phase Confirmed wild-type KRAS population	35.2 percentage of patients Interval 22.4 to 47.9
Objective Response Rate (ORR) During the Combination Therapy Phase All wild-type population	46.3 percentage of patients Interval 31.1 to 61.6
Objective Response Rate (ORR) During the Combination Therapy Phase Patients with KRAS, NRAS or BRAF mutations	0 percentage of patients Interval 0.0 to 0.0
Objective Response Rate (ORR) During the Combination Therapy Phase Whole study population	29.2 percentage of patients Interval 18.2 to 40.3

SECONDARY outcome

Timeframe: Up to 20 months

Population: Panitumumab combined with irinotecan

Per the modified Response Evaluation Criteria in Solid Tumors (m-RECIST) for target lesions and radiogically assessed (CT Scans; optionally MRI): confirmed complete (CR; Disappearance of all target lesions) or partial response (PR; At least a 30% decrease in the sum of the longest diameter of target lesions), or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the nadir longest diameter since the treatment started) while on the combination therapy treatment phase or over the entire treatment strategy. DCR = CR / PR / SD

Outcome measures

Outcome measures
Measure	Panitumumab Combined With Irinotecan n=65 Participants 69 patients were enrolled in the study. 4 patients were not eligible. 65 eligible patients were analysed
Disease Control Rate (DCR) All Wild-type population	80.5 percentage of participants Interval 68.3 to 92.6
Disease Control Rate (DCR) Overall period	63.1 percentage of participants Interval 51.3 to 74.8
Disease Control Rate (DCR) Confirmed wild-type KRAS population	66.7 percentage of participants Interval 54.1 to 79.2
Disease Control Rate (DCR) Patients with KRAS, NRAS or BRAF mutation	21.1 percentage of participants Interval 2.72 to 39.4

SECONDARY outcome

Timeframe: Up to 20 months

Population: Panitumumab combined with irinotecan

PFS was defined as time from enrollment date to date of first radiologically observed progression or death (whichever comes first) during the combination therapy phase or over the entire treatment strategy. Per the Response Evaluation Criteria in Solid Tumors (RECIST) analyzed using Kaplan-Meier methods and the quartiles and event rates at various weeks presented with 95% CIs.

Outcome measures

Outcome measures
Measure	Panitumumab Combined With Irinotecan n=65 Participants 69 patients were enrolled in the study. 4 patients were not eligible. 65 eligible patients were analysed
Progression-free Survival (PFS) Overall Period	5.5 percentage of participants Interval 3.7 to 7.6
Progression-free Survival (PFS) Confirmed wild-type KRAS population	6.3 percentage of participants Interval 3.7 to 8.7
Progression-free Survival (PFS) All wild-type population	8.7 percentage of participants Interval 5.5 to 10.4
Progression-free Survival (PFS) Patient with KRAS, NRAS or BRAF mutations	1.9 percentage of participants Interval 1.5 to 2.4

SECONDARY outcome

Timeframe: Up to 20 months

Population: Panitumumab combined with irinotecan

OS was defined as time from inclusion to death (from any cause or to the last date the patient was known to be alive) during the combination therapy phase or over the entire treatment strategy. Per the Response Evaluation Criteria in Solid Tumors (RECIST) analyzed using Kaplan-Meier methods and the quartiles and event rates at various weeks presented with 95% CIs.

Outcome measures

Outcome measures
Measure	Panitumumab Combined With Irinotecan n=65 Participants 69 patients were enrolled in the study. 4 patients were not eligible. 65 eligible patients were analysed
Overall Survival (OS) Study population	9.7 percentage of participant Interval 6.6 to 15.8
Overall Survival (OS) Confirmed wild-type KRAS population	11.9 percentage of participant Interval 6.8 to 18.2
Overall Survival (OS) All wild-type population	15.8 percentage of participant Interval 9.5 to 25.1
Overall Survival (OS) Patients with KRAS, NRAS or BRAF mutation	4.6 percentage of participant Interval 3.3 to 7.9

Adverse Events

Panitumumab + CPT11

Serious events: 10 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Panitumumab + CPT11 n=65 participants at risk 1 cycle every 14 days (J1= J15) panitumumab: Panitumumab : 6mg/kg irinotecan hydrochloride: 180mg/kg chromogenic in situ hybridization fluorescence in situ hybridization gene expression analysis laboratory biomarker analysis
Vascular disorders Occular hemorraghe	1.5% 1/65 • Number of events 1 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Cardiac disorders Tachycardia	1.5% 1/65 • Number of events 1 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Respiratory, thoracic and mediastinal disorders dyspnea	1.5% 1/65 • Number of events 1 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Nervous system disorders Epilepsy	1.5% 1/65 • Number of events 1 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
General disorders General physical health deterioration	4.6% 3/65 • Number of events 3 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Gastrointestinal disorders occlusion	6.2% 4/65 • Number of events 4 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Gastrointestinal disorders Diarrhoea	4.6% 3/65 • Number of events 3 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.

Other adverse events

Other adverse events
Measure	Panitumumab + CPT11 n=65 participants at risk 1 cycle every 14 days (J1= J15) panitumumab: Panitumumab : 6mg/kg irinotecan hydrochloride: 180mg/kg chromogenic in situ hybridization fluorescence in situ hybridization gene expression analysis laboratory biomarker analysis
Skin and subcutaneous tissue disorders skin toxicity	32.3% 21/65 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Blood and lymphatic system disorders Neutropenia	12.3% 8/65 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Gastrointestinal disorders Diarrhoea	15.4% 10/65 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.
Gastrointestinal disorders Mucositis	1.5% 1/65 • From the date of inclusion to 56 ± 3 days after the last dosing of study treatment Adverse events (AE) were collected during the treatment period and safety follow-up phases and were graded using NCI-CTCAE version 3.0.

Additional Information

Regulatory affairs

GERCOR

Phone: 00331 40 29 85 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place