Colorectal Cancer
Conditions
Keywords
panitumumab, cetuximab, KRAS wild-type
Brief summary
The purpose of this research study is to learn whether panitumumab helps treat colorectal cancer in participants who have not responded to treatment with cetuximab. Panitumumab is a human monoclonal antibody. Antibodies are proteins that recognize a foreign substance in the body and then attach themselves to it making it exposed to destruction. Panitumumab attaches itself to a protein on cancer cells called epidermal growth factor receptor or EGFR. EGFR helps cancer cells to grow, and blocking EGFR helps prevent cancer cells from growing.
Detailed description
* Panitumumab will be given to the participants through a central line. A central line is a long, thin tube (catheter) that is inserted through the skin into a large vein in the chest. This is placed by a radiologist or surgeon. * Panitumumab will be given in 4-week cycles. Panitumumab infusions will be given on days 1 and 15 of each cycle (every 2 weeks). * The following procedures will be performed on days 1 and 15 of each cycle, before each infusion: physical exam; questions about any symptoms or side effects; performance status; routine blood tests and CT or MRI (every 2 cycles). * Participants can continue to receive panitumumab until their disease gets worse or they experience unacceptable side effects.
Interventions
DRUGpanitumumab
Panitumumab is administered intravenously (IV) by an infusion pump through a peripheral line or indwelling catheter using a 0.2 or 0.22-micron in-line filter infusion set-up over 1 hour 15 minutes. The starting panitumumab dose is 6 mg/kg administered every 14 days for as long as patients are on study without evidence of disease progression or demonstrating intolerance to treatment. The total dose may be rounded up or down by no greater than 10 mg. The panitumumab dose will be calculated based on the subject's actual body weight at each visit. Panitumumab will be diluted in a minimum of 100 mL of pyrogen-free 0.9% sodium chloride solution (normal saline solution, supplied by the site). The maximum concentration of the diluted solution to be infused should not exceed 10 mg/mL.
Sponsors
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Amgen
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of colorectal adenocarcinoma and measurable disease by RECIST criteria on CT or MRI * Treated with cetuximab as part of their last treatment regimen for at least 4 weeks and must have been taken off cetuximab therapy for disease progression. Patients may or may not have been treated with 5-FU (5-Fluorouracil), oxaliplatin, irinotecan and bevacizumab. There is no maximal number of pre-existing treatment regimens. At least 2 weeks must have elapsed between previous anticancer therapy and the start of treatment on protocol, AND resolution of any skin rash related to prior treatment with epidermal growth factor receptor inhibitor * ECOG (Eastern Cooperative Oncology Group) Performance Status 0, 1 or 2 * Life expectancy of greater than 3 months * Normal organ, metabolic, and marrow function as defined in the protocol * A wild-type tumor K-RAS gene (Kirsten rat sarcoma viral oncogene homolog) as determined by sanger sequencing of exon 2 from tumor DNA * 18 years of age or older
Exclusion criteria
* History of untreated and or progression central nervous system metastases * History of another primary cancer except: curatively treated in situ cervical cancer or breast; curatively resected non-melanoma skin cancer; other primary solid tumor curatively treated with no known active disease present and no treatment administered for 3 years or more prior to enrollment * Intolerance to cetuximab leading to drug discontinuation due to rash, GI toxicity, or other grade 3 or 4 toxicities * Radiotherapy \< 14 days prior to enrollment * Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies \< 14 days before enrollment * Subjects requiring chronic use of immunosuppressive agents * Any investigational agent or therapy 30 days prior to enrollment * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with any study requirements * History of interstitial lung disease * Women who test positive for serum or urine pregnancy test or who are breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. | 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) | 3 years | 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. |
| Median Overall Survival | 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. |
| Disease Control Rate as Defined by RECIST Criteria | 3 years | 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. |
Countries
United States
Participant flow
Recruitment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Panitumumab | — |
|---|---|---|
| Age, Continuous | 54.5 years | — |
| ECOG PS 0 | 4 Participants | — |
| ECOG PS 1 | 14 Participants | — |
| ECOG PS 2 | 2 Participants | — |
| Metastatic sites Liver | 15 participants | — |
| Metastatic sites Lung | 11 participants | — |
| Metastatic sites Lymph Nodes | 9 participants | — |
| Primary tumor Colon | 17 Participants | — |
| Primary tumor Rectal | 3 Participants | — |
| Prior therapy Bevacizumab | 17 participants | — |
| Prior therapy Cetuximab | 20 participants | — |
| Prior therapy Flouropyrimidine | 20 participants | — |
| Prior therapy Irinotecan | 18 participants | — |
| Prior therapy Oxaliplatin | 19 participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 20 Participants | — |
| Sex: Female, Male Female | 10 Participants | — |
| Sex: Female, Male Male | 10 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab.
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
Time frame: 3 years
Population: One patient withdrawn for an infusion reaction prior to first re-staging CT scans.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panitumumab | Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. | Partial Response | 0 Participants |
| Panitumumab | Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. | Stable Disease | 9 Participants |
| Panitumumab | Response Rate of Single Agent Panitumumab Among Patients With KRAS Wild-type Colorectal Cancer Previously Treated With Cetuximab. | Progressive Disease | 10 Participants |
Secondary
Disease Control Rate as Defined by RECIST Criteria
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.
Time frame: 3 years
Population: One patient withdrawn for an infusion reaction prior to first re-staging CT scans.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panitumumab | Disease Control Rate as Defined by RECIST Criteria | 9 Participants |
Secondary
Median Overall Survival
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.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Median Overall Survival | 5.2 Months |
Secondary
Median Progression Free Survival (PFS)
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.
Time frame: 3 years
Population: One patient withdrawn due to an infusion reaction prior to first re-staging CT scans.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panitumumab | Median Progression Free Survival (PFS) | 1.7 Months |