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

NCT01222689 | Completed Phase 2 Results DMC

• 7 other identifiers: NCI-2011-01266CDR0000686634UCSF-10454104548598N01CM00070R21CA149939
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  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.

  Up to 2 years

• Survival at 24 Weeks

  Percent survival at 24 weeks (6 months)

  24 weeks

Secondary Outcomes (5)

• 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

• 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

• Objective Radiographic Response by RECIST Criteria

  Up to 2 years

• 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

• Number of Patients With Dose Modifications and Reason for Dose Modification.

  Up to final day of study treatment

Other Outcomes (3)

• Protein Expression Levels in Pretherapeutic Core Biopsies

  Up to 2 years

• Circulating Tumor Cell (CTC) Analysis

  Up to 2 years

• Plasma Biomarkers Potentially Predictive of Dual MEK/EGFR Inhibition

  Up to 2 years

Study Arms (1)

Treatment (erlotinib hydrochloride, selumetinib)

EXPERIMENTAL

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; Drug: selumetinib; Other: laboratory biomarker analysis

Interventions

erlotinib hydrochloride DRUG

Given PO

Also known as: CP-358,774, erlotinib, OSI-774

Treatment (erlotinib hydrochloride, selumetinib)

selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244

Treatment (erlotinib hydrochloride, selumetinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (erlotinib hydrochloride, selumetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

UCSF-Mount Zion

San Francisco, California, 94115, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Erlotinib Hydrochloride; AZD 6244

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and 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.

Results Point of Contact

• Title: Dr. Andrew Ko, MD
• Organization: university of california san francisco

Andrew.Ko@ucsf.edu

415-353-7286

Study Officials

• Andrew Ko

  UCSF-Mount Zion

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 18, 2010
• Study Start: November 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: September 1, 2014
• Last Updated: July 31, 2020
• Results First Posted: November 7, 2016

Record last verified: 2020-07

Locations

US (2)