Colorectal Cancer
Conditions
Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer
Brief summary
RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Panitumumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether erlotinib hydrochloride given together with panitumumab is more effective with or without irinotecan in treating patients with metastatic colorectal cancer. PURPOSE: This randomized phase II trial is studying giving erlotinib hydrochloride together with panitumumab to see how well it works with or without irinotecan hydrochloride as second-line therapy in treating patients with metastatic colorectal cancer.
Detailed description
OBJECTIVES: Primary * Determine the response rate in patients with metastatic colorectal cancer treated with erlotinib hydrochloride and panitumumab with versus without irinotecan hydrochloride as second-line therapy . Secondary * Determine time to disease progression and time to treatment failure in patients treated with these regimens. * Determine the safety of these regimens in these patients. * Determine the effect of these regimens on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition (exploratory). * Determine the association between KRAS mutations and response to EGFR inhibition (exploratory). OUTLINE: This is a multicenter study. Patients are stratified according to wild-type Kras tumors ( 6/6 UGT1A1 vs 6/7 UGT1A1), and are randomized to 1 of 2 treatment arms. Patients with wild-type Kras tumor 7/7 UGT1A1 receive treatment in arm III. * Arm I: Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm I. * Arm III: Patients receive erlotinib hydrochloride and panitumumab as in arm II. Skin biopsies and blood samples may be collected for further analysis. After completion of study therapy, patients are followed every 6 weeks.
Interventions
BIOLOGICALpanitumumab
Given intravenously 6mg/kg every 2 weeks
DRUGerlotinib hydrochloride
Given orally 150mg daily
DRUGirinotecan hydrochloride
Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype
Sponsors
Genentech, Inc.
OSI Pharmaceuticals
Amgen
Northwestern University
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
DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Metastatic disease * Biopsy of either the primary cancer or metastatic site required * Tumor expressing wild-type Kras mutations * Progressive disease within 3 months after treatment with first-line fluorouracil (5-FU) and oxaliplatin-based chemotherapy OR evidence of metastatic disease within 6 months of completing adjuvant therapy with 5-FU and oxaliplatin * Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques OR as ≥ 10 mm with spiral CT scan PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 6 months * ANC \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * Creatinine \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN (or \< 2 mg/dL) * AST and/or ALT \< 3 times ULN (\< 5 times ULN with liver metastases) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No concurrent malignancy requiring therapy except minor surgery for non-melanoma skin cancer removal * No interstitial lung disease with symptoms (e.g., dyspnea or cough) including any of the following significant conditions: * Parenchymal lung disease * Metastatic disease * Pulmonary infections PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior EGFR inhibitors, irinotecan hydrochloride, or other second-line chemotherapy regimens * More than 4 weeks since prior radiotherapy * No other concurrent investigational agents * No other concurrent anticancer treatment modalities (e.g., radiotherapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | At baseline and every 8 weeks during treatment until progressive disease for maximum of 51 cycles where 1 cycle = 2 weeks. | Tumor response rate will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD)of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression | At baseline and every 8 weeks during treatment until disease progression and for a maximum of 51 cycles where 1 cycle = 2 weeks | Time to disease progression will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression . Time to disease progression will be defined as the time elapsed from the day of 1st study drug administration to the day disease progression is documented or death occurs and will . Progressive Disease will be defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) : 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 to Treatment Failure | From first day of study drug treatment until the date of stopping all study drugs for any reason for a maximum of 51 cycles where 1 cycle=2weeks | Time to treatment failure will be measured as the time elapsed from the day of first study drug administration to the date a subject stops all study drugs for any reason. |
| Toxicity of the Combination of Study Drugs | Day 1 of every 2 week treatment cycle while on study treatment and 30 days after the last treatment for a maximum of 51 cycles. | Data on the toxicity of the combination of study drugs is assessed by laboratory blood draws done on day 1 of every treatment cycle and by patient report while on study treatment and up to 30 days after the last treatment. Grade 3 and grade 4 adverse events (AE) where the relationship between the AE and at least one of the study drugs were considered to be definite, probable or possible, were collected using National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). AEs are graded as: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE |
| Effect on Downstream Targets of Epidermal Growth Factor Receptor (EGFR) in Skin Rash Associated With Pharmacologic EGFR Inhibition | At baseline and at a time-point reflecting maximum rash intensity during treatment, at a maximum of 51 cycles. | Effect on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition. Skin biopsies will be performed at baseline (before the first days of treatment) and and at a time-point reflecting maximum rash intensity determined by a dermatologist. |
Countries
United States
Participant flow
Recruitment details
The study opened for accrual on July 9, 2009 with an accrual goal of up to 96 patients. The study was designed to enroll 13 patients on each arm and do an interim efficacy assessment. Accrual was suspended on March 31 2015 fand closed permanently on April 13, 2015 with 28 patients enrolled on the study.
Pre-assignment details
Subjects with either 6/6 UGT1A1 genotype or 6/7 UGT1A1 genotype will be randomized into either Arm A and Arm B. Subjects with 7/7 UGT1A1 genotype enrolled in Arm C.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Erlotinib + Panitumumab + Irinotecan Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
panitumumab: Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride: Given orally 150mg daily
irinotecan hydrochloride: Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype | 13 |
| Arm B: Erlotinib + Panitumumab Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm A.
panitumumab: Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride: Given orally 150mg daily
irinotecan hydrochloride: Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype | 13 |
| Arm C: Erlotinib + Panitumumab Patients receive erlotinib hydrochloride and panitumumab as in arm B.
panitumumab: Given intravenously 6mg/kg every 2 weeks
erlotinib hydrochloride: Given orally 150mg daily | 2 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Moved on to be Treated Cycle 5 | Adverse Event | 2 | 0 | 0 |
| Reached First Response at 8 Weeks | Adverse Event | 2 | 1 | 0 |
| Reached First Response at 8 Weeks | Progressive disease | 1 | 3 | 0 |
| Treated After Cycle 5 | Adverse Event | 0 | 0 | 1 |
| Treated After Cycle 5 | Progressive disease | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm A: Erlotinib + Panitumumab + Irinotecan | Total | Arm C: Erlotinib + Panitumumab | Arm B: Erlotinib + Panitumumab |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 9 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 19 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 23 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 25 Participants | 1 Participants | 12 Participants |
| Region of Enrollment United States | 13 Participants | 28 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 17 Participants | 2 Participants | 8 Participants |
| UGT1A1 genotyping 6/6 | 9 Participants | 16 Participants | 0 Participants | 7 Participants |
| UGT1A1 genotyping 6/7 | 4 Participants | 10 Participants | 0 Participants | 6 Participants |
| UGT1A1 genotyping 7/7 | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 13 | 10 / 10 | 1 / 2 | 3 / 3 |
| other Total, other adverse events | 13 / 13 | 10 / 10 | 2 / 2 | 3 / 3 |
| serious Total, serious adverse events | 3 / 13 | 4 / 10 | 1 / 2 | 1 / 3 |
Outcome results
Primary
Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD)
Tumor response rate will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD)of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the 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. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time frame: At baseline and every 8 weeks during treatment until progressive disease for maximum of 51 cycles where 1 cycle = 2 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: Erlotinib + Panitumumab + Irinotecan | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Stable disease | 6 Participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Complete Response | 0 Participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Partial Response | 4 Participants |
| Arm B: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Partial Response | 3 Participants |
| Arm B: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Complete Response | 1 Participants |
| Arm B: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Stable disease | 3 Participants |
| Arm C: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Stable disease | 2 Participants |
| Arm C: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Complete Response | 0 Participants |
| Arm C: Erlotinib + Panitumumab | Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD) | Partial Response | 0 Participants |
Secondary
Effect on Downstream Targets of Epidermal Growth Factor Receptor (EGFR) in Skin Rash Associated With Pharmacologic EGFR Inhibition
Effect on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition. Skin biopsies will be performed at baseline (before the first days of treatment) and and at a time-point reflecting maximum rash intensity determined by a dermatologist.
Time frame: At baseline and at a time-point reflecting maximum rash intensity during treatment, at a maximum of 51 cycles.
Population: All patient data analyzed reported together regardless of arm allocation.This outcome measure was based on optional biopsies that patients were required to consent to. Data was not collected or analyzed for this outcome measure.
Secondary
Time to Disease Progression
Time to disease progression will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression . Time to disease progression will be defined as the time elapsed from the day of 1st study drug administration to the day disease progression is documented or death occurs and will . Progressive Disease will be defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) : 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: At baseline and every 8 weeks during treatment until disease progression and for a maximum of 51 cycles where 1 cycle = 2 weeks
Population: All patient data analyzed reported together regardless of arm allocation. Data not collected and analyzed for this outcome measure.
Secondary
Time to Treatment Failure
Time to treatment failure will be measured as the time elapsed from the day of first study drug administration to the date a subject stops all study drugs for any reason.
Time frame: From first day of study drug treatment until the date of stopping all study drugs for any reason for a maximum of 51 cycles where 1 cycle=2weeks
Population: Data was not collected and analyzed for this outcome measure
Secondary
Toxicity of the Combination of Study Drugs
Data on the toxicity of the combination of study drugs is assessed by laboratory blood draws done on day 1 of every treatment cycle and by patient report while on study treatment and up to 30 days after the last treatment. Grade 3 and grade 4 adverse events (AE) where the relationship between the AE and at least one of the study drugs were considered to be definite, probable or possible, were collected using National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). AEs are graded as: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time frame: Day 1 of every 2 week treatment cycle while on study treatment and 30 days after the last treatment for a maximum of 51 cycles.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Neutrophil decrease | 7 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Sodium decrease | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Anorexia | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Rash: Hand-foot skin reaction | 4 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Leukocyte decrease | 7 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Syncope/fainting | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Rash/desquamation | 0 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Dry skin | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Phosphate decrease | 2 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Infection | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Magnesium decrease | 5 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Hemoglobin decrease | 3 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Lymphopenia | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Alkaline phosphatase decrease | 0 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Nausea | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Diarrhea | 6 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Fatigue | 1 participants |
| Arm A: Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Pruritus/itching | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Alkaline phosphatase decrease | 2 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Leukocyte decrease | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Neutrophil decrease | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Nausea | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Sodium decrease | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Fatigue | 1 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Hemoglobin decrease | 1 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Lymphopenia | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Dry skin | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Rash/desquamation | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Rash: Hand-foot skin reaction | 7 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Anorexia | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Diarrhea | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Infection | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Magnesium decrease | 4 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Phosphate decrease | 1 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Syncope/fainting | 0 participants |
| Arm B: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Pruritus/itching | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Alkaline phosphatase decrease | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Pruritus/itching | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Phosphate decrease | 3 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Leukocyte decrease | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Magnesium decrease | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Neutrophil decrease | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Nausea | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Anorexia | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Fatigue | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Rash: Hand-foot skin reaction | 2 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Infection | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Diarrhea | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Dry skin | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Hemoglobin decrease | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Lymphopenia | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Sodium decrease | 0 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Rash/desquamation | 1 participants |
| Arm C: Erlotinib + Panitumumab | Toxicity of the Combination of Study Drugs | Syncope/fainting | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Rash/desquamation | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Leukocyte decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Rash: Hand-foot skin reaction | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Anorexia | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Neutrophil decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Diarrhea | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Nausea | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Syncope/fainting | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Infection | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Phosphate decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Alkaline phosphatase decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Magnesium decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Pruritus/itching | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Fatigue | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Lymphopenia | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Dry skin | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Sodium decrease | 0 participants |
| Arm B Cross Over - Erlotinib + Panitumumab + Irinotecan | Toxicity of the Combination of Study Drugs | Hemoglobin decrease | 0 participants |
Post Hoc
Median Overall Survival
Median Overall Survival (OS) is measured from treatment initiation until death due to any cause.
Time frame: From the time of first treatment to death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Erlotinib + Panitumumab + Irinotecan | Median Overall Survival | 12.6 Months |
| Arm B: Erlotinib + Panitumumab | Median Overall Survival | 8.6 Months |
| Arm C: Erlotinib + Panitumumab | Median Overall Survival | 2.4 Months |
Post Hoc
Progression Free Survival (PFS)
Progression free survival will be measured every 8 weeks during treatment by CT or MRI scans. Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 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: At baseline and every 8 weeks during treatment until disease progression and for a maximum of 51 cycles where 1 cycle = 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Erlotinib + Panitumumab + Irinotecan | Progression Free Survival (PFS) | 4.6 Months |
| Arm B: Erlotinib + Panitumumab | Progression Free Survival (PFS) | 3.8 Months |
| Arm C: Erlotinib + Panitumumab | Progression Free Survival (PFS) | 2.4 Months |