Trial Outcomes & Findings for FOLFOXIRI Plus Panitumumab Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only (NCT NCT01226719)

Last Updated: 2015-05-27

Results Overview

The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

18 months

Results posted on

2015-05-27

Participant Flow

Participant milestones

Participant milestones
Measure	FOLFOXIRI+Panitumumab Regimen All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Overall Study STARTED	15
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

FOLFOXIRI Plus Panitumumab Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FOLFOXIRI+Panitumumab Regimen n=15 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Age, Continuous	55 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Includes all patients deemed to be evaluable for response who were evaluated for response

Outcome measures

Outcome measures
Measure	FOLFOXIRI+Panitumumab Regimen n=12 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Overall Response Rate (ORR)	75 percentage of evaluable participants

SECONDARY outcome

Timeframe: 18 months

Population: Includes patients who were surgical candidates and underwent surgery on study

To determine the rate of complete (R0) resection for patients treated with this regimen.

Outcome measures

Outcome measures
Measure	FOLFOXIRI+Panitumumab Regimen n=10 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
R0 Resection Rate	100 percentage of patients with surgery

SECONDARY outcome

Timeframe: 18 months

Population: All patients on study

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	FOLFOXIRI+Panitumumab Regimen n=15 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Progression-free Survival (PFS)	13.3 months Interval 4.2 to Upper bound of 95% confidence interval not reached at this time

SECONDARY outcome

Timeframe: 18 months

Population: All patients on study

The analyses of safety will be based on the frequency of adverse events and their severity for patients who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	FOLFOXIRI+Panitumumab Regimen n=15 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
To Determine the Acute Toxicity Produced by This Regimen. Rash	12 participants
To Determine the Acute Toxicity Produced by This Regimen. Diarrhea	9 participants
To Determine the Acute Toxicity Produced by This Regimen. Fatigue	8 participants
To Determine the Acute Toxicity Produced by This Regimen. Nausea	8 participants
To Determine the Acute Toxicity Produced by This Regimen. Mucositis	7 participants
To Determine the Acute Toxicity Produced by This Regimen. Peripheral neuropathy	6 participants
To Determine the Acute Toxicity Produced by This Regimen. Vomiting	5 participants
To Determine the Acute Toxicity Produced by This Regimen. Anorexia	4 participants
To Determine the Acute Toxicity Produced by This Regimen. Cold sensitivity	4 participants
To Determine the Acute Toxicity Produced by This Regimen. Constipation	4 participants
To Determine the Acute Toxicity Produced by This Regimen. Dehydration	4 participants
To Determine the Acute Toxicity Produced by This Regimen. Leukopenia	4 participants
To Determine the Acute Toxicity Produced by This Regimen. Anemia	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Hypokalemia	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Hypomagnesemia	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Nail changes	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Neutropenia	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Taste alteration	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Thrombocytopenia	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Weight loss	3 participants
To Determine the Acute Toxicity Produced by This Regimen. Abdominal pain	2 participants
To Determine the Acute Toxicity Produced by This Regimen. Alopecia	2 participants
To Determine the Acute Toxicity Produced by This Regimen. Depression	2 participants
To Determine the Acute Toxicity Produced by This Regimen. Dizziness	2 participants
To Determine the Acute Toxicity Produced by This Regimen. Insomnia	2 participants
To Determine the Acute Toxicity Produced by This Regimen. Alkaline phosphatase increased	1 participants
To Determine the Acute Toxicity Produced by This Regimen. ALT increased	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Anxiety	1 participants
To Determine the Acute Toxicity Produced by This Regimen. AST increased	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Asthenia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Back pain	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Blood bicarbonate increased	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Decreased ejection fraction	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Dry mouth	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Dysesthesia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Dyspepsia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Edema	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Epistaxis	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Flashers	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hand-foot syndrome	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hematochezia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hemorrhoids	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hyperpigmentation	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hypertension	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hypoalbuminemia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Hyponatremia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Infection - other	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Infusion related reaction	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Memory loss	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Oral infection	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Paraphasia	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Pruritus	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Speech impairment	1 participants
To Determine the Acute Toxicity Produced by This Regimen. Swollen tongue	1 participants

SECONDARY outcome

Timeframe: 18 months

Population: All patients on study

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

Outcome measures

Outcome measures
Measure	FOLFOXIRI+Panitumumab Regimen n=15 Participants All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Overall Survival (OS)	NA months Median overall survival and 95% confidence interval not reached at this time point - biostaticians are not reporting the lower bound of the 95% confidence interval when median overall survivial cannot be calculated

Adverse Events

FOLFOXIRI+Panitumumab Regimen

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	FOLFOXIRI+Panitumumab Regimen n=15 participants at risk All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Gastrointestinal disorders Diarrhea	13.3% 2/15 • 18 Months
General disorders Fatigue	6.7% 1/15 • 18 Months
Gastrointestinal disorders Mucositis	6.7% 1/15 • 18 Months
Gastrointestinal disorders Nausea	6.7% 1/15 • 18 Months
Skin and subcutaneous tissue disorders Rash	6.7% 1/15 • 18 Months
Gastrointestinal disorders Vomiting	6.7% 1/15 • 18 Months

Other adverse events

Other adverse events
Measure	FOLFOXIRI+Panitumumab Regimen n=15 participants at risk All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order: * Panitumumab * Oxaliplatin * Irinotecan * Leucovorin * 5-Fluorouracil Panitumumab: 6 mg/kg, 60-90 minute IV infusion every 2 weeks Oxaliplatin: 85 mg/m2, 2-hour IV infusion every 2 weeks Irinotecan: 125 mg/m2, 1-hour IV infusion every 2 weeks Leucovorin: 200 mg/m2, 2-hour IV infusion every 2 weeks 5-Fluorouracil: 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Skin and subcutaneous tissue disorders Rash	86.7% 13/15 • 18 Months
Gastrointestinal disorders Diarrhea	73.3% 11/15 • 18 Months
General disorders Fatigue	60.0% 9/15 • 18 Months
Gastrointestinal disorders Mucositis	60.0% 9/15 • 18 Months
Gastrointestinal disorders Nausea	60.0% 9/15 • 18 Months
Gastrointestinal disorders Constipation	40.0% 6/15 • 18 Months
Metabolism and nutrition disorders Dehydration	40.0% 6/15 • 18 Months
Nervous system disorders Peripheral Sensory Neuropathy	40.0% 6/15 • 18 Months
Gastrointestinal disorders Vomiting	40.0% 6/15 • 18 Months
Investigations White Blood Cell Decreased	40.0% 6/15 • 18 Months
Metabolism and nutrition disorders Anorexia	33.3% 5/15 • 18 Months
Metabolism and nutrition disorders Hypokalemia	33.3% 5/15 • 18 Months
General disorders General disorders and administration site conditions - Other, cold sensitivity	26.7% 4/15 • 18 Months
Metabolism and nutrition disorders Hypomagnesemia	26.7% 4/15 • 18 Months
Investigations Neutrophil Count Decreased	26.7% 4/15 • 18 Months
Investigations Platelet Count Decreased	26.7% 4/15 • 18 Months
Gastrointestinal disorders Abdominal Pain	20.0% 3/15 • 18 Months
Investigations Alanine aminotransferase increased	20.0% 3/15 • 18 Months
Blood and lymphatic system disorders Anemia	20.0% 3/15 • 18 Months
Psychiatric disorders Anxiety	20.0% 3/15 • 18 Months
Nervous system disorders Dizziness	20.0% 3/15 • 18 Months
Nervous system disorders Dysgeusia	20.0% 3/15 • 18 Months
Psychiatric disorders Insomnia	20.0% 3/15 • 18 Months
Investigations Weight loss	20.0% 3/15 • 18 Months
Skin and subcutaneous tissue disorders Alopecia	13.3% 2/15 • 18 Months
Investigations Aspartate aminotransferase increased	13.3% 2/15 • 18 Months
General disorders Chills	13.3% 2/15 • 18 Months
Psychiatric disorders Depression	13.3% 2/15 • 18 Months
Gastrointestinal disorders Dry mouth	13.3% 2/15 • 18 Months
Nervous system disorders Dysesthesia	13.3% 2/15 • 18 Months
General disorders Fever	13.3% 2/15 • 18 Months
Gastrointestinal disorders Gastrointestinal disorders - Other, bloody stools	13.3% 2/15 • 18 Months
Nervous system disorders Headache	13.3% 2/15 • 18 Months
Gastrointestinal disorders Hemorrhoids	13.3% 2/15 • 18 Months
Metabolism and nutrition disorders Hyperglycemia	13.3% 2/15 • 18 Months
Vascular disorders Hypertension	13.3% 2/15 • 18 Months
Skin and subcutaneous tissue disorders Nail discoloration	13.3% 2/15 • 18 Months
Nervous system disorders Nervous system disorders - Other, speech impairment	13.3% 2/15 • 18 Months
Gastrointestinal disorders Rectal Pain	13.3% 2/15 • 18 Months
Infections and infestations Upper Respiratory Infection	13.3% 2/15 • 18 Months
Investigations Alkaline phosphatase increased	6.7% 1/15 • 18 Months
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.7% 1/15 • 18 Months
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 1/15 • 18 Months
Musculoskeletal and connective tissue disorders Back Pain	6.7% 1/15 • 18 Months
Renal and urinary disorders Bladder spasm	6.7% 1/15 • 18 Months
Eye disorders Blurred vision	6.7% 1/15 • 18 Months
Injury, poisoning and procedural complications Burn	6.7% 1/15 • 18 Months
Eye disorders Conjunctivitis	6.7% 1/15 • 18 Months
Respiratory, thoracic and mediastinal disorders Cough	6.7% 1/15 • 18 Months
Eye disorders Dry eye	6.7% 1/15 • 18 Months
General disorders Edema limbs	6.7% 1/15 • 18 Months
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 1/15 • 18 Months
Eye disorders Eye disorders - Other, blepharitis	6.7% 1/15 • 18 Months
Eye disorders Flashing lights	6.7% 1/15 • 18 Months
Injury, poisoning and procedural complications Fracture	6.7% 1/15 • 18 Months
Gastrointestinal disorders Gastroesophageal reflux disease	6.7% 1/15 • 18 Months
Gastrointestinal disorders Gastrointestinal disorders - Other, enlarged tongue	6.7% 1/15 • 18 Months
Gastrointestinal disorders Gastrointestinal disorders - Other, stomatitis	6.7% 1/15 • 18 Months
Gastrointestinal disorders Gastrointestinal Pain	6.7% 1/15 • 18 Months
Musculoskeletal and connective tissue disorders Generalized muscle weakness	6.7% 1/15 • 18 Months
Infections and infestations Gum infection	6.7% 1/15 • 18 Months
Respiratory, thoracic and mediastinal disorders Hoarseness	6.7% 1/15 • 18 Months
Metabolism and nutrition disorders Hypoalbuminemia	6.7% 1/15 • 18 Months
Metabolism and nutrition disorders Hypoglycemia	6.7% 1/15 • 18 Months
Metabolism and nutrition disorders Hyponatremia	6.7% 1/15 • 18 Months
Metabolism and nutrition disorders Hypophosphatemia	6.7% 1/15 • 18 Months
Vascular disorders Hypotension	6.7% 1/15 • 18 Months
Infections and infestations Infections and infestations - Other, pneumonia	6.7% 1/15 • 18 Months
Infections and infestations Infections and infestations - Other, unknown	6.7% 1/15 • 18 Months
General disorders infusion related reaction	6.7% 1/15 • 18 Months
Investigations Investigations - Other, blood bicarbonate decreased	6.7% 1/15 • 18 Months
Investigations Investigations - Other, blood bicarbonate increased	6.7% 1/15 • 18 Months
Infections and infestations Joint infection	6.7% 1/15 • 18 Months
Infections and infestations Laryngitis	6.7% 1/15 • 18 Months
Nervous system disorders Memory impairment	6.7% 1/15 • 18 Months
Musculoskeletal and connective tissue disorders Myalgia	6.7% 1/15 • 18 Months
Gastrointestinal disorders Oral Pain	6.7% 1/15 • 18 Months
Musculoskeletal and connective tissue disorders Pain in Extremity	6.7% 1/15 • 18 Months
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	6.7% 1/15 • 18 Months
Infections and infestations Paronychia	6.7% 1/15 • 18 Months
Skin and subcutaneous tissue disorders Pruritus	6.7% 1/15 • 18 Months
Gastrointestinal disorders Rectal hemorrhage	6.7% 1/15 • 18 Months
Renal and urinary disorders Renal and urinary disorders - Other, acute renal insufficiency	6.7% 1/15 • 18 Months
Infections and infestations Sepsis	6.7% 1/15 • 18 Months
Infections and infestations Sinusitis	6.7% 1/15 • 18 Months
Skin and subcutaneous tissue disorders Skin hyperpigmentation	6.7% 1/15 • 18 Months
Infections and infestations Skin infection	6.7% 1/15 • 18 Months
Respiratory, thoracic and mediastinal disorders Sore Throat	6.7% 1/15 • 18 Months
Gastrointestinal disorders Toothache	6.7% 1/15 • 18 Months

Additional Information

John D Hainsworth, MD

Sarah Cannon Research Institute

Phone: 1-877-691-7274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
Publication restrictions are in place

Restriction type: OTHER