Metastatic Colorectal Cancer
Conditions
Keywords
colon, rectal, liver, AMG 954 (Panitumumab), DEXAMETHASONE, FLOXURIDINE, FLUOROURACIL, IRINOTECAN (CPT-11) CAMPTOSAR, LEUCOVORIN, 10-137
Brief summary
The purpose of this study is to see if Panitumumab plus the other treatments will increase the time of remission. Remission means that there is no sign of the cancer.
Interventions
DRUGpanitumumab
All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1. All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization to panitumumab 6 mg/kg day 15 and 29 Each cycle repeats every 36 days for a total of 6 cycles
DRUGRandomization to No Panitumumab
All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1. All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization (to no panitumumab) Each cycle repeats every 36 days for a total of 6 cycles
Sponsors
Amgen
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed at MSKCC. * Completely resected hepatic metastases without current evidence of other metastatic disease. * Lab values ≤ 14 days prior to treatment start: * WBC ≥ 3.0 K/uL * ANC \> 1.5 K/uL * Platelets ≥ 100,000/uL * Creatinine \<1.5 mg/dL * HGB ≥ 9 gm/dL Renal function (≤ 14 days prior to treatment start). * Creatinine ≤1.5 mg/dL or creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault method as follows: * Male creatinine clearance = (140 -age in years) x (weight in Kg) / (serum Cr in mg/dl x 72) * Female creatinine clearance = (140 - age in years) x (weight in Kg) x 0.85 / (serum Cr in mg/dl x 72) (use of creatinine clearance per protocol based on chemotherapy regimen) Hepatic function, as follows: (≤ 14 days prior to treatment start) * Aspartate aminotransferase (AST) (≤ 5 x ULN) * Alanine aminotransferase (ALT) (≤ 5 x ULN) * Total Bilirubin ≤ 1.5 mg/dl * Magnesium ≥ lower limit of normal (≤ 48 hours prior to treatment start.) * Calcium ≥ lower limit of normal (≤ 48 hours prior to treatment start.) * Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to registration to this study. \[Note: no chemotherapy to be given after resection of liver lesions prior to treatment on this study.\] * Any investigational agent is acceptable if administered ≤ 30 days before registration * KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for Karnofsky) * Histologically confirmed all RAS wild type. * Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis (Prior to
Exclusion criteria
* Patients \< 18 years of age. * Prior radiation to the liver (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration.) * Active infection, ascites, hepatic encephalopathy. * Prior treatment with HAI FUDR. * Patients who have had prior anti EGFR antibody therapy inhibitors and who have not responded to this treatment will be excluded. However, patients who have responded to prior anti-EGFR therapy are eligible.) * Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of child-bearing potential must have negative pregnancy test ≤ 72 hours before registration). * If a patient has any serious medical problems which may preclude receiving this type of treatment. * Patients with current evidence of hepatitis A, B, C (ie, active hepatitis) * Patients with history or known presence of primary CNS tumors, seizures not well controlled with standard medical therapy, or history of stroke will also be excluded. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Panitumumab. * Serious or non-healing active wound, ulcer, or bone fracture. * History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. * Patients who have a diagnosis of Gilbert's disease. * History of other malignancy, except: * Malignancy treated with curative intent and with no known active disease present for ≥ 3 years prior to registration and felt to be at low risk for recurrence by the treating physician * Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease * Adequately treated cervical carcinoma in situ without evidence of disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Recurrence Free Survival for Colorectal Cancer Participants With Resected Liver Metastases | 15 months | to determine if panitumumab with Hepatic Arterial Infusion (HAI) in combination with systemic chemotherapy can increase the recurrence free survival (RFS) for colorectal cancer patients with resected liver metastases |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Evaluated for Toxicity as Per the NCI Common Toxicity Criteria | 2 years | Toxicities will be recorded as adverse events on the Adverse Event case report form and must be graded using The National Cancer Institute's Common Toxicity Criteria (CTC)version 4.0 with the exception of skin- or nail-related toxicities, which must be graded using CTC version 3.0 with modifications |
| Participant Survival | 2 years | — |
| Number of Participants With Tumor Tissue Expression of Predictive Makers | 2 years | (such as NRAS, BRAF, PIK3CA, AKT1 and MEK1), and correlate with patient progression and survival following therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomization to Panitumumab Patients whose liver metastases have been completely resected will be randomized Arm A will receive Panitumumab in addition to HAI FUDR/Dexamethasone plus systemic CPT-11/5FU/LV
panitumumab: All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1.
All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization to panitumumab 6 mg/kg day 15 and 29 Each cycle repeats every 36 days for a total of 6 cycles | 37 |
| Randomization to No Panitumumab Patients whose liver metastases have been completely resected will be randomized and patients randomized to Arm B will receive HAI FUDR/Dex plus systemic CPT-11/5FU/LV alone.
Randomization to No Panitumumab: All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1.
All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization (to no panitumumab) Each cycle repeats every 36 days for a total of 6 cycles | 38 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Randomization to Panitumumab | Randomization to No Panitumumab | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 53 years | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 34 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 34 Participants | 27 Participants | 61 Participants |
| Region of Enrollment United States | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 25 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 15 / 37 | 27 / 38 |
| other Total, other adverse events | 27 / 37 | 26 / 38 |
| serious Total, serious adverse events | 14 / 37 | 6 / 38 |
Outcome results
Primary
Participants With Recurrence Free Survival for Colorectal Cancer Participants With Resected Liver Metastases
to determine if panitumumab with Hepatic Arterial Infusion (HAI) in combination with systemic chemotherapy can increase the recurrence free survival (RFS) for colorectal cancer patients with resected liver metastases
Time frame: 15 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Randomization to Panitumumab | Participants With Recurrence Free Survival for Colorectal Cancer Participants With Resected Liver Metastases | 69 percentage of participants |
| Randomization to No Panitumumab | Participants With Recurrence Free Survival for Colorectal Cancer Participants With Resected Liver Metastases | 47 percentage of participants |
Secondary
Number of Participants Evaluated for Toxicity as Per the NCI Common Toxicity Criteria
Toxicities will be recorded as adverse events on the Adverse Event case report form and must be graded using The National Cancer Institute's Common Toxicity Criteria (CTC)version 4.0 with the exception of skin- or nail-related toxicities, which must be graded using CTC version 3.0 with modifications
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomization to Panitumumab | Number of Participants Evaluated for Toxicity as Per the NCI Common Toxicity Criteria | 37 Participants |
| Randomization to No Panitumumab | Number of Participants Evaluated for Toxicity as Per the NCI Common Toxicity Criteria | 38 Participants |
Secondary
Number of Participants With Tumor Tissue Expression of Predictive Makers
(such as NRAS, BRAF, PIK3CA, AKT1 and MEK1), and correlate with patient progression and survival following therapy.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | NRAS | 1 Participants |
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | BRAF | 0 Participants |
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | PIK3CA | 3 Participants |
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | AKT1 | 0 Participants |
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | MEK1 | 0 Participants |
| Randomization to Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | Participants without predictive tumor markers | 33 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | MEK1 | 0 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | NRAS | 1 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | AKT1 | 0 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | BRAF | 2 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | Participants without predictive tumor markers | 27 Participants |
| Randomization to No Panitumumab | Number of Participants With Tumor Tissue Expression of Predictive Makers | PIK3CA | 8 Participants |
Secondary
Participant Survival
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomization to Panitumumab | Participant Survival | Alive | 22 Participants |
| Randomization to Panitumumab | Participant Survival | Dead | 15 Participants |
| Randomization to No Panitumumab | Participant Survival | Alive | 11 Participants |
| Randomization to No Panitumumab | Participant Survival | Dead | 27 Participants |