Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01222689
Collaborator
(none)
46
2
1
46
23
0.5

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving selumetinib and erlotinib hydrochloride together works in treating patients with locally advanced or metastatic pancreatic cancer that is refractory to chemotherapy. Selumetinib and erlotinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or Disease Intervention/Treatment Phase
  • Drug: erlotinib hydrochloride
  • Drug: selumetinib
  • Other: laboratory biomarker analysis
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess overall survival (as measured by median survival and proportion of patients alive at 24 weeks) in patients with advanced pancreatic cancer who have received one prior line of systemic therapy when treated with the combination of AZD6244 (selumetinib) and erlotinib (erlotinib hydrochloride).
SECONDARY OBJECTIVES:
  1. Progression-free survival (median progression-free survival [PFS] and proportion of patients with PFS at 12 and 24 weeks).

  2. Cancer antigen (CA)19-9 biomarker response (defined as a 50% decline in serum CA19-9 level from baseline in patients with > 2 x upper limit of normal [ULN] CA19-9 measurement).

  3. Objective radiographic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

  4. Safety and toxicity profile of the combination of AZ6244 and erlotinib.

OUTLINE:

Patients receive selumetinib orally (PO) once daily (QD) and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-3 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of AZD6244 Plus Erlotinib for the Second-Line Treatment of Advanced Pancreatic Adenocarcinoma
Study Start Date :
Nov 1, 2010
Actual Primary Completion Date :
Apr 1, 2013
Actual Study Completion Date :
Sep 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (erlotinib hydrochloride, selumetinib)

Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: erlotinib hydrochloride
Given PO
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
  • Drug: selumetinib
    Given PO
    Other Names:
  • ARRY-142886
  • AZD6244
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Up to 2 years]

      Survival will be calculated according to the method of Kaplan and Meier. Both actual and estimated probability of being alive (along with a 95% confidence interval) at 24 weeks (6 months) and for any multiple of 6 months will be calculated for which the number of uncensored subjects is not smaller than 10.

    2. Survival at 24 Weeks [24 weeks]

      Percent survival at 24 weeks (6 months)

    Secondary Outcome Measures

    1. Progression-free Survival (PFS) [From first dose of study treatment to the date of objective progression, or death due to cancer or unknown cause, or to the date of withdrawal from the trial from unknown reasons, assessed up to 2 years]

      Calculated according to the method of Kaplan and Meier. Actual and estimated probability of being alive and progression-free, along with a 95% confidence interval, will be calculated. Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(Macdonald et al.):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used. Progressive Disease is defined as a 20% or higher increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

    2. CA19-9 Biomarker Response (Defined as a 50% Decline in Serum CA19-9 Level From Baseline in Patients With > 2 x ULN CA19-9 Measurement) [Up to 2 years]

      The proportion of patients with CA19-9 response.

    3. Objective Radiographic Response by RECIST Criteria [Up to 2 years]

      Patient's best overall response will be tabulated by level; proportions of complete response (CR) and of CR+partial response will be calculated along with 95% confidence intervals. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR, >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.

    4. Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after completion of study treatment]

      Tabulation of type of adverse events (AE) and the incidence of grade 3 and 4 for each AE

    5. Number of Patients With Dose Modifications and Reason for Dose Modification. [Up to final day of study treatment]

      Tabulation of the reasons for dose modification with number of patients

    Other Outcome Measures

    1. Protein Expression Levels in Pretherapeutic Core Biopsies [Up to 2 years]

      Logistic regression models will be used to associate baseline protein markers and best objective response. Cox models will be used to associate baseline protein markers with overall and progression-free survival. Each selected protein markers will be evaluated individually and ranked by the corresponding p-values. Combinations of markers will also be explored.

    2. Circulating Tumor Cell (CTC) Analysis [Up to 2 years]

      The association between baseline CTC numbers, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response will be evaluated. The association between expression level of protein markers in CTC with biopsy samples using Pearson's correlation and by unsupervised hierarchical clustering of samples using Pearson correlation as the distance metric will be assessed. Association of longitudinal protein markers in CTC with patient OS will be evaluated using the joint models of longitudinal observations.

    3. Plasma Biomarkers Potentially Predictive of Dual MEK/EGFR Inhibition [Up to 2 years]

      The association between candidate plasma biomarkers of interest, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response. Specifically, correlation of the relative change in allelic frequency of mutations present in both pre-treatment and on-treatment blood samples versus percent change in CA19-9.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Histologically or cytologically proven adenocarcinoma of the pancreas

    • Patients must have locally advanced unresectable disease not amenable to curative resection or extrapancreatic metastases; patients must have EITHER radiographically measurable disease (defined as at least one lesion that can be accurately measured in at least one dimension [longest diameter to be recorded] as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography [CT] scan) AND/OR a serum CA19-9 measurement > 2 x ULN

    • One prior line of systemic therapy for advanced disease (locally advanced or metastatic)

    • The following represent acceptable examples meeting the definition of one prior line of therapy:

    • Gemcitabine as a single agent or in combination with other agents; patients receiving (a) gemcitabine initially alone, with the eventual addition of a second agent; or (b) gemcitabine as part of a combination regimen, followed by gemcitabine alone; are eligible

    • A non-gemcitabine-based regimen, including (but not limited to) leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) or any combination of components therein

    • Treatment as part of a clinical trial involving cytotoxic agents, small molecule inhibitors, monoclonal antibodies, and/or immunomodulatory agents

    • For patients with locally advanced disease, prior radiation to the primary tumor is allowable as long as there is clear evidence of disease progression (either radiographic locoregional disease progression and/or a rising CA19-9 level); patients may have received chemotherapy both concurrently and/or sequentially with (either before or after) the radiation and still be eligible for the study, as this would be considered all part of the same course of treatment

    • Treatment given in the adjuvant setting (radiation and/or chemotherapy, given either concurrently or sequentially) does not count as prior therapy as long as progressive disease occurs > 6 months following completion of treatment

    • Life expectancy of greater than 8 weeks

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    • Absolute neutrophil count (ANC) >= 1500/uL

    • Platelet count >= 100,000/uL

    • International normalized ratio (INR) =< 1.5 (except those subjects who are receiving full-dose warfarin)

    • Total bilirubin =< 2.0 mg/dL

    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal for subjects

    • Serum creatinine of =< 2.0 mg/dL

    • Pregnancy test for women of childbearing potential (serum or urine beta-human chorionic gonadotropin [HCG])

    • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

    • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for four weeks after dosing with AZD6244 ceases; women of child-bearing potential must have a negative pregnancy test prior to entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; please note that the AZD6244 manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle

    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:
    • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

    • Patients may not be receiving any other investigational agents

    • Patients with known brain metastases should be excluded from this clinical trial

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 (or its excipient Captisol) or erlotinib

    • Previous mitogen-activated protein kinase kinase (MEK) or epidermal growth factor receptor (EGFR) inhibitor use

    • Patients with corrected QT (QTc) interval > 480 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that (i) meets New York Heart Association (NYHA) class III and IV definitions or (ii) is demonstrated by an left ventricular (LV) ejection fraction < 55% on baseline echocardiogram, are excluded

    • Required use of a concomitant medication that can prolong the QT interval

    • There are potential interactions between erlotinib and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and CYP3A4 promoters; although caution and careful monitoring are recommended when use of these compounds is necessary, use of these compounds does not exclude patients from participating in this trial

    • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

    • Pregnant women are excluded from this study; therefore, a negative pregnancy test is required for women of childbearing potential; breastfeeding should be discontinued if the mother is treated with AZD6244

    • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSF-Mount Zion San Francisco California United States 94115
    2 Ohio State University Medical Center Columbus Ohio United States 43210

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Andrew Ko, UCSF-Mount Zion

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01222689
    Other Study ID Numbers:
    • NCI-2011-01266
    • NCI-2011-01266
    • CDR0000686634
    • UCSF-10454
    • 10454
    • 8598
    • N01CM00070
    • R21CA149939
    First Posted:
    Oct 18, 2010
    Last Update Posted:
    Jul 31, 2020
    Last Verified:
    Jul 1, 2020

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Period Title: Overall Study
    STARTED 46
    COMPLETED 46
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib by mouth (PO) every day (QD) and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Overall Participants 46
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    67
    Sex: Female, Male (Count of Participants)
    Female
    24
    52.2%
    Male
    22
    47.8%
    Region of Enrollment (participants) [Number]
    United States
    46
    100%
    Prior chemotherapy (participants) [Number]
    Gemcitabine-based
    34
    73.9%
    FOLFIRINOX
    10
    21.7%
    Other
    2
    4.3%
    Prior surgery (participants) [Number]
    Number [participants]
    14
    30.4%
    Prior radiation (participants) [Number]
    Number [participants]
    7
    15.2%
    Elevated baseline Cancer Antigen 19-9(CA19-9) > 2x Upper Limit of Normal (ULN) (participants) [Number]
    Number [participants]
    34
    73.9%
    Eastern Cooperative Oncology Group (ECOG) performance status (participants) [Number]
    status = 0
    32
    69.6%
    status = 1
    14
    30.4%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival (OS)
    Description Survival will be calculated according to the method of Kaplan and Meier. Both actual and estimated probability of being alive (along with a 95% confidence interval) at 24 weeks (6 months) and for any multiple of 6 months will be calculated for which the number of uncensored subjects is not smaller than 10.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 46
    Median (95% Confidence Interval) [months]
    7.3
    2. Secondary Outcome
    Title Progression-free Survival (PFS)
    Description Calculated according to the method of Kaplan and Meier. Actual and estimated probability of being alive and progression-free, along with a 95% confidence interval, will be calculated. Response and progression are evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(Macdonald et al.):205-216, 2000]. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used. Progressive Disease is defined as a 20% or higher increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
    Time Frame From first dose of study treatment to the date of objective progression, or death due to cancer or unknown cause, or to the date of withdrawal from the trial from unknown reasons, assessed up to 2 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 46
    Median (95% Confidence Interval) [months]
    1.9
    3. Secondary Outcome
    Title CA19-9 Biomarker Response (Defined as a 50% Decline in Serum CA19-9 Level From Baseline in Patients With > 2 x ULN CA19-9 Measurement)
    Description The proportion of patients with CA19-9 response.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Patients with baseline levels > 2 x ULN CA19-9 measurement
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 34
    Number [percentage of participants]
    38
    82.6%
    4. Secondary Outcome
    Title Objective Radiographic Response by RECIST Criteria
    Description Patient's best overall response will be tabulated by level; proportions of complete response (CR) and of CR+partial response will be calculated along with 95% confidence intervals. Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR, >= 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    There were no complete or patial responses by RECIST (stable disease, partial response, or complete response) amongst the 46 participants
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 46
    Complete Response (CR)
    0
    0%
    Complete+Partial Response
    0
    0%
    5. Secondary Outcome
    Title Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
    Description Tabulation of type of adverse events (AE) and the incidence of grade 3 and 4 for each AE
    Time Frame Up to 30 days after completion of study treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 46
    Rash
    10
    Diarrhea
    6
    Nausea/vomiting
    4
    Fatigue
    3
    AST/ALT elevation
    4
    Anorexia
    0
    Anemia
    5
    Dysgeusia
    0
    Eye disorders
    0
    Pruritus
    0
    Hypertension
    6
    Thrombocytopenia
    1
    Leukopenia/neutropenia
    1
    Thromboembolic event (incl. cerebral)
    3
    Elevated creatinine
    0
    6. Other Pre-specified Outcome
    Title Protein Expression Levels in Pretherapeutic Core Biopsies
    Description Logistic regression models will be used to associate baseline protein markers and best objective response. Cox models will be used to associate baseline protein markers with overall and progression-free survival. Each selected protein markers will be evaluated individually and ranked by the corresponding p-values. Combinations of markers will also be explored.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Data was not collected.
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 0
    7. Other Pre-specified Outcome
    Title Circulating Tumor Cell (CTC) Analysis
    Description The association between baseline CTC numbers, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response will be evaluated. The association between expression level of protein markers in CTC with biopsy samples using Pearson's correlation and by unsupervised hierarchical clustering of samples using Pearson correlation as the distance metric will be assessed. Association of longitudinal protein markers in CTC with patient OS will be evaluated using the joint models of longitudinal observations.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Data was not collected.
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 0
    8. Other Pre-specified Outcome
    Title Plasma Biomarkers Potentially Predictive of Dual MEK/EGFR Inhibition
    Description The association between candidate plasma biomarkers of interest, their longitudinal changes, and patient outcomes as measured by OS, PFS, and radiographic and biomarker response. Specifically, correlation of the relative change in allelic frequency of mutations present in both pre-treatment and on-treatment blood samples versus percent change in CA19-9.
    Time Frame Up to 2 years

    Outcome Measure Data

    Analysis Population Description
    Patients who had non-germline mutations (circulating cell-free DNA) represented in both their pre-treatment blood and on-treatment blood samples.
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 24
    Number [R^2]
    0.1369
    9. Primary Outcome
    Title Survival at 24 Weeks
    Description Percent survival at 24 weeks (6 months)
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 46
    Number [percentage of participants]
    58
    126.1%
    10. Secondary Outcome
    Title Number of Patients With Dose Modifications and Reason for Dose Modification.
    Description Tabulation of the reasons for dose modification with number of patients
    Time Frame Up to final day of study treatment

    Outcome Measure Data

    Analysis Population Description
    Numbers in tabulation total to more than 18 because patients often had 2 or more reasons that prompted dose reduction. For example: Nausea/Vomiting + diarrhea (3), fatigue + diarrhea (2), rash + hypertension (1), rash + diarrhea (1), fatigue + Nausea/Vomiting (1)
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    Measure Participants 18
    RASH
    8
    17.4%
    Diarrhea
    7
    15.2%
    NAUSEA/VOMITING
    5
    10.9%
    Fatigue
    3
    6.5%
    Hypertension
    1
    2.2%
    TRANSAMINITIS
    1
    2.2%
    UNKNOWN
    1
    2.2%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Treatment (Erlotinib Hydrochloride, Selumetinib)
    Arm/Group Description Patients receive selumetinib PO QD and erlotinib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
    All Cause Mortality
    Treatment (Erlotinib Hydrochloride, Selumetinib)
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Treatment (Erlotinib Hydrochloride, Selumetinib)
    Affected / at Risk (%) # Events
    Total 22/46 (47.8%)
    Blood and lymphatic system disorders
    edema 1/46 (2.2%)
    Platelet count decrease 1/46 (2.2%)
    anemia 2/46 (4.3%)
    Cardiac disorders
    Cardiac disorder 1/46 (2.2%)
    Gastrointestinal disorders
    Acites 3/46 (6.5%)
    Nausea 3/46 (6.5%)
    Vomiting 4/46 (8.7%)
    fatigue 11/46 (23.9%)
    Diarrhea 1/46 (2.2%)
    Esophageal varicies hemorrhage 1/46 (2.2%)
    Abdominal distension 2/46 (4.3%)
    Abdominal pain 3/46 (6.5%)
    Obstruction gastric 1/46 (2.2%)
    Small intestine ulcer 1/46 (2.2%)
    General disorders
    Pain 1/46 (2.2%)
    Chills 1/46 (2.2%)
    Fever 2/46 (4.3%)
    Infections and infestations
    Vaginal infection 1/46 (2.2%)
    Abdominal Infection 1/46 (2.2%)
    Injury, poisoning and procedural complications
    Spinal Fracture 1/46 (2.2%)
    Fall 1/46 (2.2%)
    Investigations
    Alanine Aminotransferase increae 1/46 (2.2%)
    Alkaline phosphastase increase 1/46 (2.2%)
    blood bilirubin increase 1/46 (2.2%)
    Aspartate aminotransferase increase 1/46 (2.2%)
    Metabolism and nutrition disorders
    dehydration 4/46 (8.7%)
    Hyponatremia 2/46 (4.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify - disease progr 7/46 (15.2%)
    Psychiatric disorders
    Confusion - acute dementia 1/46 (2.2%)
    Delusion - acute dementia 1/46 (2.2%)
    Renal and urinary disorders
    Acute Kidney Injury 3/46 (6.5%)
    Respiratory, thoracic and mediastinal disorders
    Dypsnea 1/46 (2.2%)
    Other (Not Including Serious) Adverse Events
    Treatment (Erlotinib Hydrochloride, Selumetinib)
    Affected / at Risk (%) # Events
    Total 46/46 (100%)
    Blood and lymphatic system disorders
    Anemia 13/46 (28.3%)
    Elevated white blood cell count 1/46 (2.2%)
    Cardiac disorders
    Sinus tachycardia 1/46 (2.2%)
    Eye disorders
    Blurred vision 3/46 (6.5%)
    Dry eye 1/46 (2.2%)
    Left eye irritation 1/46 (2.2%)
    Chalazion 1/46 (2.2%)
    Eye pain 1/46 (2.2%)
    Floaters 2/46 (4.3%)
    Photophobia 1/46 (2.2%)
    Watering eyes 1/46 (2.2%)
    Gastrointestinal disorders
    Abdominal distension 3/46 (6.5%)
    Abdominal pain 14/46 (30.4%)
    Ascites 4/46 (8.7%)
    Bloating 2/46 (4.3%)
    Constipation 6/46 (13%)
    Diarrhea 36/46 (78.3%)
    Dry Mouth 4/46 (8.7%)
    Dyspepsia 5/46 (10.9%)
    Esophageal varices hemorrhage 1/46 (2.2%)
    Flatulence 2/46 (4.3%)
    Gastroesophageal reflux disease 1/46 (2.2%)
    Gastrointestinal disorders, Other, Specify 5/46 (10.9%)
    Mucositis oral 3/46 (6.5%)
    Nausea 25/46 (54.3%)
    Obstruction gastric 1/46 (2.2%)
    Oral dysesthesia 1/46 (2.2%)
    Oral hemorrhage 1/46 (2.2%)
    Small intestine ulcer 1/46 (2.2%)
    Vomiting 20/46 (43.5%)
    Lower gastrointestinal hemorrhage 1/46 (2.2%)
    General disorders
    Chills 6/46 (13%)
    Edema face 1/46 (2.2%)
    Edema limbs 9/46 (19.6%)
    Fatigue 26/46 (56.5%)
    Fever 7/46 (15.2%)
    Localized edema 2/46 (4.3%)
    Neck edema 1/46 (2.2%)
    Non-cardiac chest pain 2/46 (4.3%)
    Pain 2/46 (4.3%)
    Death NOS 4/46 (8.7%)
    Infections and infestations
    Abdominal infection 1/46 (2.2%)
    Bladder infection 1/46 (2.2%)
    Infections and infestations - Other, specify 1/46 (2.2%)
    Lung infection 1/46 (2.2%)
    Nail infection 1/46 (2.2%)
    Paronychia 3/46 (6.5%)
    Skin infection 2/46 (4.3%)
    Urinary tract infection 2/46 (4.3%)
    Vaginal infection 1/46 (2.2%)
    Injury, poisoning and procedural complications
    Bruising 2/46 (4.3%)
    Fall 2/46 (4.3%)
    Spinal fracture 1/46 (2.2%)
    Investigations
    Alanine aminotransferase increase 13/46 (28.3%)
    Alkaline phosphatase increased 13/46 (28.3%)
    Aspartate aminotransferase increased 21/46 (45.7%)
    Blood bilirubin increased 4/46 (8.7%)
    Creatinine increased 4/46 (8.7%)
    INR increased 3/46 (6.5%)
    Investigations - Other, specify 1/46 (2.2%)
    Lymphocyte count decreased 6/46 (13%)
    Neutrophil count decreased 1/46 (2.2%)
    Neutrophil count decreased 5/46 (10.9%)
    Weight loss 5/46 (10.9%)
    White blood cell decreased 3/46 (6.5%)
    Metabolism and nutrition disorders
    Anorexia 1/46 (2.2%)
    Dehydration 6/46 (13%)
    Hyperglycemia 5/46 (10.9%)
    Hypoalbuminemia 9/46 (19.6%)
    Hypocalcemia 3/46 (6.5%)
    Hypoglycemia 2/46 (4.3%)
    Hypokalemia 6/46 (13%)
    Hyponatremia 4/46 (8.7%)
    Hypophosphatemia 1/46 (2.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 1/46 (2.2%)
    Nervous system disorders
    Dizziness 3/46 (6.5%)
    Dysgeusia 11/46 (23.9%)
    Nervous system disorders - Other, specify 1/46 (2.2%)
    Peripheral sensory neuropathy 2/46 (4.3%)
    Somnolence 1/46 (2.2%)
    Stroke 11/46 (23.9%)
    Tremor 1/46 (2.2%)
    Psychiatric disorders
    Confusion 2/46 (4.3%)
    Delusions 1/46 (2.2%)
    Insomnia 2/46 (4.3%)
    Renal and urinary disorders
    Acute kidney injury 4/46 (8.7%)
    Hematuria 1/46 (2.2%)
    Urinary frequency 1/46 (2.2%)
    Epistaxis 2/46 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/46 (4.3%)
    Dyspnea 4/46 (8.7%)
    Pleural effusion 1/46 (2.2%)
    Respiratory, thoracic and mediastinal disorders - Other, specify 2/46 (4.3%)
    Skin and subcutaneous tissue disorders
    Alopecia 4/46 (8.7%)
    Body odor 1/46 (2.2%)
    Dry skin 17/46 (37%)
    Hirsutism 1/46 (2.2%)
    Palmar-plantar erythrodysesthesia syndrome 1/46 (2.2%)
    Periorbital edema 3/46 (6.5%)
    Pruritus 10/46 (21.7%)
    Rash acneiform 28/46 (60.9%)
    Rash maculo-papular 15/46 (32.6%)
    Scalp pain 1/46 (2.2%)
    Skin and subcutaneous tissue disorders - Other, specify 3/46 (6.5%)
    Skin ulceration 2/46 (4.3%)
    Vascular disorders
    Flushing 1/46 (2.2%)
    Hypertension 8/46 (17.4%)
    Hypotension 1/46 (2.2%)
    Thromboembolic event 3/46 (6.5%)

    Limitations/Caveats

    In this single arm, nonrandomized study, an inherent selection bias was likely due to enrollment of patients with favorable disease biology, who had undergone prior resection and fare better compared with those with stage IV disease at diagnosis.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Dr. Andrew Ko, MD
    Organization university of california san francisco
    Phone 415-353-7286
    Email Andrew.Ko@ucsf.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01222689
    Other Study ID Numbers:
    • NCI-2011-01266
    • NCI-2011-01266
    • CDR0000686634
    • UCSF-10454
    • 10454
    • 8598
    • N01CM00070
    • R21CA149939
    First Posted:
    Oct 18, 2010
    Last Update Posted:
    Jul 31, 2020
    Last Verified:
    Jul 1, 2020