Trial Outcomes & Findings for Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (NCT NCT01222689)

NCT ID: NCT01222689

Last Updated: 2020-07-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2020-07-31

Participant Flow

Participant milestones

Participant milestones
Measure
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. erlotinib hydrochloride: Given PO selumetinib: Given PO laboratory biomarker analysis: Correlative studies
Overall Study
STARTED
46
Overall Study
COMPLETED
46
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Age, Continuous
67 years
n=5 Participants
Sex: Female, Male
Female
24 Participants
n=5 Participants
Sex: Female, Male
Male
22 Participants
n=5 Participants
Region of Enrollment
United States
46 participants
n=5 Participants
Prior chemotherapy
Gemcitabine-based
34 participants
n=5 Participants
Prior chemotherapy
FOLFIRINOX
10 participants
n=5 Participants
Prior chemotherapy
Other
2 participants
n=5 Participants
Prior surgery
14 participants
n=5 Participants
Prior radiation
7 participants
n=5 Participants
Elevated baseline Cancer Antigen 19-9(CA19-9) > 2x Upper Limit of Normal (ULN)
34 participants
n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status
status = 0
32 participants
n=5 Participants
Eastern Cooperative Oncology Group (ECOG) performance status
status = 1
14 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Overall Survival (OS)
7.3 months
Interval 5.2 to 8.0

PRIMARY outcome

Timeframe: 24 weeks

Percent survival at 24 weeks (6 months)

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Survival at 24 Weeks
58 percentage of participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Progression-free Survival (PFS)
1.9 months
Interval 1.4 to 3.3

SECONDARY outcome

Timeframe: Up to 2 years

Population: Patients with baseline levels \> 2 x ULN CA19-9 measurement

The proportion of patients with CA19-9 response.

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=34 Participants
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
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)
38 percentage of participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: There were no complete or patial responses by RECIST (stable disease, partial response, or complete response) amongst the 46 participants

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.

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Objective Radiographic Response by RECIST Criteria
Complete Response (CR)
0 participants
Objective Radiographic Response by RECIST Criteria
Complete+Partial Response
0 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 Participants
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
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Anemia
5 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Dysgeusia
0 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Eye disorders
0 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Rash
10 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Diarrhea
6 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Nausea/vomiting
4 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Fatigue
3 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
AST/ALT elevation
4 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Anorexia
0 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Pruritus
0 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Hypertension
6 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Thrombocytopenia
1 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Leukopenia/neutropenia
1 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Thromboembolic event (incl. cerebral)
3 events
Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Elevated creatinine
0 events

SECONDARY outcome

Timeframe: Up to final day of study treatment

Population: 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)

Tabulation of the reasons for dose modification with number of patients

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=18 Participants
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
Number of Patients With Dose Modifications and Reason for Dose Modification.
RASH
8 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
Diarrhea
7 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
NAUSEA/VOMITING
5 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
Fatigue
3 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
Hypertension
1 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
TRANSAMINITIS
1 participants
Number of Patients With Dose Modifications and Reason for Dose Modification.
UNKNOWN
1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 2 years

Population: Data was not collected.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 2 years

Population: Data was not collected.

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 2 years

Population: Patients who had non-germline mutations (circulating cell-free DNA) represented in both their pre-treatment blood and on-treatment blood samples.

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.

Outcome measures

Outcome measures
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=24 Participants
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
Plasma Biomarkers Potentially Predictive of Dual MEK/EGFR Inhibition
0.1369 R^2

Adverse Events

Treatment (Erlotinib Hydrochloride, Selumetinib)

Serious events: 22 serious events
Other events: 46 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 participants at risk
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
Gastrointestinal disorders
Acites
6.5%
3/46
Gastrointestinal disorders
Nausea
6.5%
3/46
Gastrointestinal disorders
Vomiting
8.7%
4/46
Blood and lymphatic system disorders
edema
2.2%
1/46
Gastrointestinal disorders
fatigue
23.9%
11/46
Blood and lymphatic system disorders
Platelet count decrease
2.2%
1/46
Metabolism and nutrition disorders
dehydration
8.7%
4/46
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify - disease progr
15.2%
7/46
Renal and urinary disorders
Acute Kidney Injury
6.5%
3/46
Injury, poisoning and procedural complications
Spinal Fracture
2.2%
1/46
Gastrointestinal disorders
Diarrhea
2.2%
1/46
Gastrointestinal disorders
Esophageal varicies hemorrhage
2.2%
1/46
Cardiac disorders
Cardiac disorder
2.2%
1/46
General disorders
Pain
2.2%
1/46
Blood and lymphatic system disorders
anemia
4.3%
2/46
Gastrointestinal disorders
Abdominal distension
4.3%
2/46
Gastrointestinal disorders
Abdominal pain
6.5%
3/46
Investigations
Alanine Aminotransferase increae
2.2%
1/46
Investigations
Alkaline phosphastase increase
2.2%
1/46
Investigations
blood bilirubin increase
2.2%
1/46
Investigations
Aspartate aminotransferase increase
2.2%
1/46
Infections and infestations
Vaginal infection
2.2%
1/46
Metabolism and nutrition disorders
Hyponatremia
4.3%
2/46
General disorders
Chills
2.2%
1/46
General disorders
Fever
4.3%
2/46
Respiratory, thoracic and mediastinal disorders
Dypsnea
2.2%
1/46
Infections and infestations
Abdominal Infection
2.2%
1/46
Injury, poisoning and procedural complications
Fall
2.2%
1/46
Gastrointestinal disorders
Obstruction gastric
2.2%
1/46
Psychiatric disorders
Confusion - acute dementia
2.2%
1/46
Psychiatric disorders
Delusion - acute dementia
2.2%
1/46
Gastrointestinal disorders
Small intestine ulcer
2.2%
1/46

Other adverse events

Other adverse events
Measure
Treatment (Erlotinib Hydrochloride, Selumetinib)
n=46 participants at risk
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
Blood and lymphatic system disorders
Anemia
28.3%
13/46
Blood and lymphatic system disorders
Elevated white blood cell count
2.2%
1/46
Cardiac disorders
Sinus tachycardia
2.2%
1/46
Eye disorders
Blurred vision
6.5%
3/46
Eye disorders
Dry eye
2.2%
1/46
Eye disorders
Left eye irritation
2.2%
1/46
Eye disorders
Chalazion
2.2%
1/46
Eye disorders
Eye pain
2.2%
1/46
Eye disorders
Floaters
4.3%
2/46
Eye disorders
Photophobia
2.2%
1/46
Eye disorders
Watering eyes
2.2%
1/46
Gastrointestinal disorders
Abdominal distension
6.5%
3/46
Gastrointestinal disorders
Abdominal pain
30.4%
14/46
Gastrointestinal disorders
Ascites
8.7%
4/46
Gastrointestinal disorders
Bloating
4.3%
2/46
Gastrointestinal disorders
Constipation
13.0%
6/46
Gastrointestinal disorders
Diarrhea
78.3%
36/46
Gastrointestinal disorders
Dry Mouth
8.7%
4/46
Gastrointestinal disorders
Dyspepsia
10.9%
5/46
Gastrointestinal disorders
Esophageal varices hemorrhage
2.2%
1/46
Gastrointestinal disorders
Flatulence
4.3%
2/46
Gastrointestinal disorders
Gastroesophageal reflux disease
2.2%
1/46
Gastrointestinal disorders
Gastrointestinal disorders, Other, Specify
10.9%
5/46
Gastrointestinal disorders
Mucositis oral
6.5%
3/46
Gastrointestinal disorders
Nausea
54.3%
25/46
Gastrointestinal disorders
Obstruction gastric
2.2%
1/46
Gastrointestinal disorders
Oral dysesthesia
2.2%
1/46
Gastrointestinal disorders
Oral hemorrhage
2.2%
1/46
Gastrointestinal disorders
Small intestine ulcer
2.2%
1/46
Gastrointestinal disorders
Vomiting
43.5%
20/46
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
2.2%
1/46
General disorders
Chills
13.0%
6/46
General disorders
Edema face
2.2%
1/46
General disorders
Edema limbs
19.6%
9/46
General disorders
Fatigue
56.5%
26/46
General disorders
Fever
15.2%
7/46
General disorders
Localized edema
4.3%
2/46
General disorders
Neck edema
2.2%
1/46
General disorders
Non-cardiac chest pain
4.3%
2/46
General disorders
Pain
4.3%
2/46
General disorders
Death NOS
8.7%
4/46
Infections and infestations
Abdominal infection
2.2%
1/46
Infections and infestations
Bladder infection
2.2%
1/46
Infections and infestations
Infections and infestations - Other, specify
2.2%
1/46
Infections and infestations
Lung infection
2.2%
1/46
Infections and infestations
Nail infection
2.2%
1/46
Infections and infestations
Paronychia
6.5%
3/46
Infections and infestations
Skin infection
4.3%
2/46
Infections and infestations
Urinary tract infection
4.3%
2/46
Infections and infestations
Vaginal infection
2.2%
1/46
Injury, poisoning and procedural complications
Bruising
4.3%
2/46
Injury, poisoning and procedural complications
Fall
4.3%
2/46
Injury, poisoning and procedural complications
Spinal fracture
2.2%
1/46
Investigations
Alanine aminotransferase increase
28.3%
13/46
Investigations
Alkaline phosphatase increased
28.3%
13/46
Investigations
Aspartate aminotransferase increased
45.7%
21/46
Investigations
Blood bilirubin increased
8.7%
4/46
Investigations
Creatinine increased
8.7%
4/46
Investigations
INR increased
6.5%
3/46
Investigations
Investigations - Other, specify
2.2%
1/46
Investigations
Lymphocyte count decreased
13.0%
6/46
Investigations
Neutrophil count decreased
10.9%
5/46
Investigations
Weight loss
10.9%
5/46
Investigations
White blood cell decreased
6.5%
3/46
Metabolism and nutrition disorders
Anorexia
2.2%
1/46
Metabolism and nutrition disorders
Dehydration
13.0%
6/46
Metabolism and nutrition disorders
Hyperglycemia
10.9%
5/46
Metabolism and nutrition disorders
Hypoalbuminemia
19.6%
9/46
Metabolism and nutrition disorders
Hypocalcemia
6.5%
3/46
Metabolism and nutrition disorders
Hypoglycemia
4.3%
2/46
Metabolism and nutrition disorders
Hypokalemia
13.0%
6/46
Metabolism and nutrition disorders
Hyponatremia
8.7%
4/46
Metabolism and nutrition disorders
Hypophosphatemia
2.2%
1/46
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
2.2%
1/46
Nervous system disorders
Dizziness
6.5%
3/46
Nervous system disorders
Dysgeusia
23.9%
11/46
Nervous system disorders
Nervous system disorders - Other, specify
2.2%
1/46
Nervous system disorders
Peripheral sensory neuropathy
4.3%
2/46
Nervous system disorders
Somnolence
2.2%
1/46
Nervous system disorders
Stroke
23.9%
11/46
Nervous system disorders
Tremor
2.2%
1/46
Psychiatric disorders
Confusion
4.3%
2/46
Psychiatric disorders
Delusions
2.2%
1/46
Psychiatric disorders
Insomnia
4.3%
2/46
Renal and urinary disorders
Acute kidney injury
8.7%
4/46
Renal and urinary disorders
Hematuria
2.2%
1/46
Renal and urinary disorders
Urinary frequency
2.2%
1/46
Respiratory, thoracic and mediastinal disorders
Cough
4.3%
2/46
Respiratory, thoracic and mediastinal disorders
Dyspnea
8.7%
4/46
Renal and urinary disorders
Epistaxis
4.3%
2/46
Respiratory, thoracic and mediastinal disorders
Pleural effusion
2.2%
1/46
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
4.3%
2/46
Skin and subcutaneous tissue disorders
Alopecia
8.7%
4/46
Skin and subcutaneous tissue disorders
Body odor
2.2%
1/46
Skin and subcutaneous tissue disorders
Dry skin
37.0%
17/46
Skin and subcutaneous tissue disorders
Hirsutism
2.2%
1/46
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
2.2%
1/46
Skin and subcutaneous tissue disorders
Periorbital edema
6.5%
3/46
Skin and subcutaneous tissue disorders
Pruritus
21.7%
10/46
Skin and subcutaneous tissue disorders
Rash acneiform
60.9%
28/46
Skin and subcutaneous tissue disorders
Rash maculo-papular
32.6%
15/46
Skin and subcutaneous tissue disorders
Scalp pain
2.2%
1/46
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
6.5%
3/46
Skin and subcutaneous tissue disorders
Skin ulceration
4.3%
2/46
Vascular disorders
Flushing
2.2%
1/46
Vascular disorders
Hypertension
17.4%
8/46
Vascular disorders
Hypotension
2.2%
1/46
Vascular disorders
Thromboembolic event
6.5%
3/46

Additional Information

Dr. Andrew Ko, MD

university of california san francisco

Phone: 415-353-7286

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60