Adenocarcinoma of the Lung, Non-small Cell Lung Cancer
Conditions
Keywords
Adenocarcinoma of the Lung, Non-small Cell Lung Cancer
Brief summary
Hsp90 inhibitor AUY922 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of Hsp90 inhibitor AUY922 when given together with erlotinib hydrochloride and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer.
Detailed description
This is a phase I, dose-escalation study of Hsp90 inhibitor AUY922 followed by a phase II study. Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.
Interventions
DRUGerlotinib hydrochloride
Given orally
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREneedle biopsy
Undergo image-guided needle biopsy (correlative studies)
GENETICmutation analysis
Correlative studies
OTHERpharmacological study
Correlative studies
Sponsors
Robert H. Lurie Cancer Center
Northwestern University
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
* All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q) * Radiographic progression by RECIST during treatment with erlotinib/gefitinib * Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time * Measurable (RECIST) indicator lesion not previously irradiated * Must have undergone a biopsy after the development of acquired resistance * Karnofsky Performance Status \>= 70% OR ECOG/WHO Performance Status 0-1 * Signed informed consent * Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =\< 24 months ago) and women \< 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for \> 24 months * Total bilirubin =\< 1.5 x Upper Limit of Normal (ULN) * AST/SGOT and ALT/SGPT =\< 3.0 x ULN, or =\< 5.0 x ULN if liver metastasis present * Absolute neutrophil count (ANC) \>= 1.5 x10\^9/L * Hemoglobin (Hgb) \>= 9g/dL * Platelets (plts) \>= 100 x 10\^9/L * Serum creatinine =\< 1.5 x ULN or 24 hour clearance \>= 50 mL/min
Exclusion criteria
* Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids * Prior treatment with any HSP90 inhibitor compounds * Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed) * Palliative radiation within 2 weeks * Unresolved diarrhea \>= CTCAE grade 2 * Pregnant or lactating women * Women of childbearing potential (WCBP) (i.e. women able to become pregnant) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile); male patients whose partners are WCBP not using double-barrier methods of contraception * Acute or chronic liver or renal disease * Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol * Major surgery =\< 2 weeks prior to randomization or who have not recovered from such therapy * History (or family history) of long QT syndrome * Mean QTc \>= 450 msec on baseline ECG * History of clinically manifested ischemic heart disease =\< 6 months prior to study start * History of heart failure or left ventricular (LV) dysfunction (LVEF =\< 45%) by MUGA or ECG * Clinically significant resting bradycardia (\< 50 beats per minute) * Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemi-block (LAHB); ST segment elevation or depression \> 1mm, or 2nd (Mobitz II), or 3rd degree AV block * History ventricular tachycardia * Other clinically significant heart disease including congestive heart failure (New York Heart Association class III/IV) or uncontrolled hypertension (\> 160/90 despite intensive medical management) * Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 * Known diagnosis of HIV infection (HIV testing is not mandatory) * Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention * Patients who are receiving warfarin (Coumadin®) will be excluded unless =\< 2 mg/d, with an INR \< 1.5 * Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | During the first 4 weeks of treatment for each patient. | To determine the maximally tolerated dose (MTD), and recommended phase II dose of AUY922 when given in combination with erlotinib for patients with acquired resistance to erlotinib. (Phase I) Escalation of dose will be in a 3+3 design. If no dose limiting toxicities (DLTs) are seen in 3 patients enrolled at that dose level, then dose will be escalated to the next dose level and the next 3 patients will be enrolled at that dose. Alternatively, if 1 DLT is seen in 3 patients at that dose level, 3 more patients will be added at that same dose level. If 1 DLT is seen in 6 patients at that dose level, MTD will be determined to be at that dose. If more than 1 DLT is seen at that dose level, then the prior lower dose level will be the considered the MTD. DLT is defined as any of the following related to the investigational agent: Death and grade 3 and 4 specific hematological and non-hematological toxicities defined in the protocol. |
| Overall Response Rate (ORR), Defined as Complete Response(CR) + Partial Response (PR) Using the Modified RECIST 1.1 Criteria for All Patients Treated at Dose of 70mg/m2 AUG922 | At 8 weeks from treatment initiation | Overall response rate (ORR) will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR), defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (Phase II) | From the time of first treatment with AUY922 to disease progression for up to 2 years post treatment | Median Progression Free Survival (PFS) will be calculated from time of treatment initiation until the first documentation of progressive disease. Patients will be considered to have progressive disease when CT scan or MRI show 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. |
| Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment for up to 2 years and half years | To characterize the toxicity profile for the combination of erlotinib and AUY922. Toxicity data will be collected every week for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following: 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 |
| Overall Survival Among Patients With Acquired Resistance With T790M Mutations (Phase II) | From the time of first treatment with AUY922 to death, followed for up to 2 years | Overall Survival (OS) will be measured from treatment initiation until death due to any cause for patients with acquired resistance with T790M mutations in the phase II portion of the study. |
| Overall Survival (Phase II) | From the time of first treatment with AUY922 to death, followed up to 2 years post treatment | Overall survival (OS) is defined as the time from treatment initiation until death due to any cause. |
| Incidence of Reported Adverse Events in Phase I | At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment, for up to 2 years and half years | Adverse events will be collected weekly for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following: 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 |
Countries
United States
Participant flow
Recruitment details
The study opened for accrual on March 28, 2011 with an accrual goal of up to 30 patients in phase I and 25 patients in phase II. 18 patients were enrolled treated in phase I and 19 patients treated in phase II. The study was closed permanently on May 6, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive Hsp90 inhibitor AUY922 IV over 1 hour once weekly and oral erlotinib hydrochloride once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride: Given orally
Hsp90 inhibitor AUY922: Given IV
laboratory biomarker analysis: Correlative studies
needle biopsy: Undergo image-guided needle biopsy (correlative studies)
mutation analysis: Correlative studies
pharmacological study: Correlative studies | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Confirmed Response at 8 Weeks | Adverse Event | 0 | 0 | 0 | 0 | 1 | 2 |
| Confirmed Response at 8 Weeks | Progressive disease | 0 | 0 | 1 | 1 | 3 | 7 |
| Confirmed Response at 8 Weeks | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
| Continued Treatment After 8 Weeks | Adverse Event | 0 | 0 | 0 | 0 | 2 | 1 |
| Continued Treatment After 8 Weeks | Progressive disease | 1 | 1 | 1 | 1 | 0 | 0 |
| Continued Treatment After 8 Weeks | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 |
| Reached First Response at 4 Weeks | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Reached First Response at 4 Weeks | Patient not treated on study | 0 | 0 | 0 | 0 | 0 | 1 |
| Survival Follow up for Two Years | Death | 3 | 2 | 2 | 3 | 6 | 13 |
| Survival Follow up for Two Years | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 2 |
| Survival Follow up for Two Years | stopped being followed as study closed | 0 | 0 | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Region of Enrollment United States | 38 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 13 / 19 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 19 / 19 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 1 / 3 | 1 / 3 | 2 / 6 | 1 / 19 |
Outcome results
Primary
Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I)
To determine the maximally tolerated dose (MTD), and recommended phase II dose of AUY922 when given in combination with erlotinib for patients with acquired resistance to erlotinib. (Phase I) Escalation of dose will be in a 3+3 design. If no dose limiting toxicities (DLTs) are seen in 3 patients enrolled at that dose level, then dose will be escalated to the next dose level and the next 3 patients will be enrolled at that dose. Alternatively, if 1 DLT is seen in 3 patients at that dose level, 3 more patients will be added at that same dose level. If 1 DLT is seen in 6 patients at that dose level, MTD will be determined to be at that dose. If more than 1 DLT is seen at that dose level, then the prior lower dose level will be the considered the MTD. DLT is defined as any of the following related to the investigational agent: Death and grade 3 and 4 specific hematological and non-hematological toxicities defined in the protocol.
Time frame: During the first 4 weeks of treatment for each patient.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | 0 Number of DLTs seen |
| Cohort 2 - 25 mg/m2AUY922+150 mg Daily Erlotinib | Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | 0 Number of DLTs seen |
| Cohort 3 - 37.5 mg/m2 AUY922+150 mg Daily Erlotinib | Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | 0 Number of DLTs seen |
| Cohort 4 - 55 mg/m2 AUY922+150 mg Daily Erlotinib | Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | 0 Number of DLTs seen |
| Cohort 5 - 70 mg/m2 AUY922+150 mg Daily Erlotinib | Maximally Tolerated Dose (MTD) of AUY922 and Erlotinib Treatment Combination (Phase I) | 1 Number of DLTs seen |
Primary
Overall Response Rate (ORR), Defined as Complete Response(CR) + Partial Response (PR) Using the Modified RECIST 1.1 Criteria for All Patients Treated at Dose of 70mg/m2 AUG922
Overall response rate (ORR) will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan or MRI: Complete response (CR) defined as disappearance of all target lesions. Partial Response (PR), defined as \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) defined as having at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions
Time frame: At 8 weeks from treatment initiation
Population: All patients that were treated at the MTD dose of 70mg/m2 AUG922 IV were evaluable for this outcome measure (This includes patients treated in cohort 5 of phase I and all patients treated in phase II of the study)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Overall Response Rate (ORR), Defined as Complete Response(CR) + Partial Response (PR) Using the Modified RECIST 1.1 Criteria for All Patients Treated at Dose of 70mg/m2 AUG922 | 4 Participants |
Secondary
Incidence of Reported Adverse Events in Phase I
Adverse events will be collected weekly for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following: 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: At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment, for up to 2 years and half years
Population: Most frequent adverse events for patients treated with 25 to 55mg/m2 dose of AUY9222.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Hypomagnesemia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Diarrhea | 11 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Skin rash | 9 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Hyperglycemia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Night blindness | 3 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Hypoalbuminemia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Fatigue | 8 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Elevated AST | 1 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Nausea | 8 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Hyponatremia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Elevated bilirubin | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Elevated ALT | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Myalgias/arthralgias | 5 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Visual complaints | 4 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Vomiting | 4 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Elevated ALP | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Decreased leukocytes | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | hypokalemia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Pruritis/dry skin | 4 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Hypocalcemia | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | anemia | 2 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Mucositis | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Decreased lymphocytes | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Decreased platelets | 0 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Incidence of Reported Adverse Events in Phase I | Decreased neutrophils | 0 participants |
Secondary
Overall Survival Among Patients With Acquired Resistance With T790M Mutations (Phase II)
Overall Survival (OS) will be measured from treatment initiation until death due to any cause for patients with acquired resistance with T790M mutations in the phase II portion of the study.
Time frame: From the time of first treatment with AUY922 to death, followed for up to 2 years
Population: No data was collected or analyzed for this outcome measure. There is no data to report. IND was withdrawn before the studies anticipated termination date.
Secondary
Overall Survival (Phase II)
Overall survival (OS) is defined as the time from treatment initiation until death due to any cause.
Time frame: From the time of first treatment with AUY922 to death, followed up to 2 years post treatment
Population: 25 of the patients were treated at the MTD and were evaluable for progression free survival. Data was collected up until September 30 2014 when study was closed permanently and no further data was collected for patients survival due to IND withdrawal.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Overall Survival (Phase II) | 7.4 Months |
Secondary
Progression-free Survival (Phase II)
Median Progression Free Survival (PFS) will be calculated from time of treatment initiation until the first documentation of progressive disease. Patients will be considered to have progressive disease when CT scan or MRI show 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: From the time of first treatment with AUY922 to disease progression for up to 2 years post treatment
Population: 25 of the patients were treated at the MTD and were evaluable for progression free survival. Data was collected up until September 30 2014 when study was closed permanently and no further data was collected for patients survival due to IND withdrawal.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Progression-free Survival (Phase II) | 1.7 Months |
Secondary
Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II)
To characterize the toxicity profile for the combination of erlotinib and AUY922. Toxicity data will be collected every week for the first 28 day cycle and then every two weeks during treatment and up to 28 days after the last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 4.0 (CTCAE v4.0). In general adverse events (AEs) will be graded according to the following: 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: At weeks 1 through 4 and then every 2 weeks during treatment and 30 days post last treatment for up to 2 years and half years
Population: Toxicity collected from all patients treated at the MTD of 70mg/m2 AUY922. 6 patients in phase I and 19 patients in phase II were treated at this dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Diarrhea | 24 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Skin rash | 16 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hyperglycemia | 23 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Night blindness | 18 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hypoalbuminemia | 21 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Fatigue | 11 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Elevated AST | 17 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Nausea | 9 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hyponatremia | 17 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Elevated bilirubin | 16 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Elevated ALT | 14 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Myalgias/arthralgias | 9 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Visual complaints | 10 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Vomiting | 8 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Elevated APL | 10 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Decreased leukocytes | 10 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hypokalemia | 10 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Pruritis/dry skin | 5 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hypocalcemia | 8 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Anemia | 4 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Mucositis | 6 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Decreased lymphocytes | 6 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Decreased platelets | 6 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Hypomagnesemia | 6 participants |
| Cohort 1 - 25 mg/m2 AUY922+75 mg Daily Erlotinib | Toxicity as Assessed by NCI CTCAE Version 4.00 When AUG922 Administered at Its MTD (Phase I and II) | Decreased neutrophils | 5 participants |