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Adenocarcinoma of the PancreasPhase 2NCT01222689

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

A Phase 2 study testing erlotinib hydrochloride, selumetinib and laboratory biomarker analysis in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
erlotinib hydrochloride, selumetinib and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
2 sitesUnited States
Study dates
Nov 2010to Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • UCSF-Mount Zion

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Phase 2 Study of AZD6244 Plus Erlotinib for the Second-Line Treatment of Advanced Pancreatic Adenocarcinoma

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.

Read the 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).

II. 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).

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

IV. 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.

Being tested
erlotinib hydrochloride, selumetinib, laboratory biomarker analysis
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    Given PO

  • selumetinibDrug

    Also called ARRY-142886, AZD6244

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01222689
Study groupRoleWhat they receive
Treatment (erlotinib hydrochloride, selumetinib)ExperimentalPatients 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.
Receives: Drug: erlotinib hydrochloride; Drug: selumetinib; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 years

  2. Survival at 24 Weeks

    Percent survival at 24 weeks (6 months)

    Measured: 24 weeks

Secondary outcomes (5)

  1. Progression-free Survival (PFS)

    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).

    Measured: 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

  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)

    The proportion of patients with CA19-9 response.

    Measured: Up to 2 years

  3. Objective Radiographic Response by RECIST Criteria

    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.

    Measured: Up to 2 years

  4. Incidence of Toxicities Graded Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

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

    Measured: Up to 30 days after completion of study treatment

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

    Tabulation of the reasons for dose modification with number of patients

    Measured: Up to final day of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionApr 2013
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01222689
Sponsor's protocol ID
NCI-2011-01266
Other IDs
NCI-2011-01266, CDR0000686634, UCSF-10454, 10454, 8598, N01CM00070, R21CA149939
Status last verified
Jul 2020
First submitted
15 Oct 2010
Last updated
31 Jul 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing erlotinib hydrochloride, selumetinib and laboratory biomarker analysis in people with Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01222689.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.

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