Trial Outcomes & Findings for Panitumumab in Cetuximab Refractory KRAS Wild-Type Colorectal Cancer (NCT NCT00842257)

Last Updated: 2017-05-16

Results Overview

The response rate of single agent panitumumab among patients with KRAS wild-type (Kirsten rat sarcoma viral oncogene homolog) colorectal cancer previously treated with cetuximab. Inclusive of three patients with clinical progression prior to first re-staging CT scans. Response rate evaluated using RECIST (Response Evaluation Criteria In Solid Tumors). Best overall response is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). RECIST: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

3 years

Results posted on

2017-05-16

Participant Flow

Subjects identified by their treating oncologist in the Gastrointestinal Cancer Clinics at Massachusetts General Hospital and Dana-Farber Cancer Institute, all therapy options are discussed (including participation in this trial).

Participant milestones

Participant milestones
Measure	Panitumumab Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Overall Study STARTED	20
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Panitumumab Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Overall Study Adverse Event	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panitumumab n=20 Participants Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Age, Continuous	54.5 years n=20 Participants
Sex: Female, Male Female	10 Participants n=20 Participants
Sex: Female, Male Male	10 Participants n=20 Participants
Region of Enrollment United States	20 Participants n=20 Participants
ECOG PS 0	4 Participants n=20 Participants
ECOG PS 1	14 Participants n=20 Participants
ECOG PS 2	2 Participants n=20 Participants
Primary tumor Colon	17 Participants n=20 Participants
Primary tumor Rectal	3 Participants n=20 Participants
Metastatic sites Liver	15 participants n=20 Participants
Metastatic sites Lung	11 participants n=20 Participants
Metastatic sites Lymph Nodes	9 participants n=20 Participants
Prior therapy Cetuximab	20 participants n=20 Participants
Prior therapy Flouropyrimidine	20 participants n=20 Participants
Prior therapy Oxaliplatin	19 participants n=20 Participants
Prior therapy Irinotecan	18 participants n=20 Participants
Prior therapy Bevacizumab	17 participants n=20 Participants

PRIMARY outcome

Timeframe: 3 years

Population: One patient withdrawn for an infusion reaction prior to first re-staging CT scans.

Outcome measures

Outcome measures
Measure	Panitumumab n=19 Participants Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. Partial Response	0 Participants
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. Stable Disease	9 Participants
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. Progressive Disease	10 Participants

SECONDARY outcome

Timeframe: 3 years

Population: One patient withdrawn due to an infusion reaction prior to first re-staging CT scans.

The duration of time from start of treatment to time of radiologic disease progression per RECIST or death, or otherwise the date of last tumor assessment. Median PFS was calculated using Kaplan Meier suvival analysis. Progressive disease is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Panitumumab n=19 Participants Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Median Progression Free Survival (PFS)	1.7 Months Interval 0.5 to 3.7

SECONDARY outcome

Timeframe: 3 years

The duration of time from start of treatment to time of death or otherwise the date of last tumor assessment. Median survival was calculated using Kaplan Meier suvival analysis.

Outcome measures

Outcome measures
Measure	Panitumumab n=20 Participants Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Median Overall Survival	5.2 Months Interval 1.0 to 18.2

SECONDARY outcome

Timeframe: 3 years

Population: One patient withdrawn for an infusion reaction prior to first re-staging CT scans.

Disease Control Rate as defined by RECIST criteria. The number patients achieving stable disease, partial response, or complete response at some point during follow-up.

Outcome measures

Outcome measures
Measure	Panitumumab n=19 Participants Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Disease Control Rate as Defined by RECIST Criteria	9 Participants

Adverse Events

Panitumumab

Serious events: 0 serious events

Other events: 20 other events

Deaths: 20 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Panitumumab n=20 participants at risk Panitumumab administered by a central line infusion over 1 hour 15 minutes on days 1 and 15 of each 4 week cycle. The starting panitumumab dose is 6 mg/kg, the total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose is calculated based on the subject's actual body weight at each visit. Panitumumab is diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution. The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Gastrointestinal disorders Abdomen- pain	25.0% 5/20 • Number of events 6 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Alkaline phosphatase	30.0% 6/20 • Number of events 11 • 3 Years Participants were assessed for toxicity before each dose.
Immune system disorders Allergic reaction	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Alopecia	15.0% 3/20 • Number of events 4 • 3 Years Participants were assessed for toxicity before each dose.
Gastrointestinal disorders Anorexia	30.0% 6/20 • Number of events 7 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders AST- SGOT	25.0% 5/20 • Number of events 8 • 3 Years Participants were assessed for toxicity before each dose.
Musculoskeletal and connective tissue disorders Back- pain	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Bicarbonate	15.0% 3/20 • Number of events 4 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Bilirubin	25.0% 5/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
Gastrointestinal disorders Constipation	40.0% 8/20 • Number of events 8 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Creatinine	15.0% 3/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
Gastrointestinal disorders Dehydration	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Gastrointestinal disorders Diarrhea w/o prior colostomy	15.0% 3/20 • Number of events 4 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Dry skin	25.0% 5/20 • Number of events 11 • 3 Years Participants were assessed for toxicity before each dose.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 4/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
Blood and lymphatic system disorders Edema limb	15.0% 3/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Erythema multiforme	10.0% 2/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
General disorders Fatigue	75.0% 15/20 • Number of events 22 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Hand-foot reaction	10.0% 2/20 • Number of events 4 • 3 Years Participants were assessed for toxicity before each dose.
Blood and lymphatic system disorders Hemoglobin	35.0% 7/20 • Number of events 8 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hemoglobinuria	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypercalcemia	10.0% 2/20 • Number of events 3 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hyperglycemia	25.0% 5/20 • Number of events 7 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hyperkalemia	25.0% 5/20 • Number of events 7 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypermagnesemia	25.0% 5/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypoalbuminemia	30.0% 6/20 • Number of events 8 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypoglycemia	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypokalemia	15.0% 3/20 • Number of events 3 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypomagnesemia	40.0% 8/20 • Number of events 15 • 3 Years Participants were assessed for toxicity before each dose.
Metabolism and nutrition disorders Hypophosphatemia	40.0% 8/20 • Number of events 13 • 3 Years Participants were assessed for toxicity before each dose.
General disorders Insomnia	20.0% 4/20 • Number of events 4 • 3 Years Participants were assessed for toxicity before each dose.
Blood and lymphatic system disorders Lymphopenia	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.
Nervous system disorders Neuropathy-sensory	25.0% 5/20 • Number of events 5 • 3 Years Participants were assessed for toxicity before each dose.
General disorders Pain-other	15.0% 3/20 • Number of events 3 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Rash/desquamation	20.0% 4/20 • Number of events 7 • 3 Years Participants were assessed for toxicity before each dose.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	40.0% 8/20 • Number of events 18 • 3 Years Participants were assessed for toxicity before each dose.
General disorders Weight loss	10.0% 2/20 • Number of events 2 • 3 Years Participants were assessed for toxicity before each dose.

Additional Information

Dr. David Patrick Ryan, Chief, Hem/Onc

Massachusetts General Hospital

Phone: 617-974-4545

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place