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Acinar Cell Adenocarcinoma of the PancreasPhase 1NCT00981162

Sorafenib Tosylate and Everolimus in Treating Patients With Advanced Solid Tumors and Metastatic Pancreatic Cancer That Does Not Respond to Gemcitabine Hydrochloride

A Phase 1 study testing sorafenib tosylate, everolimus and laboratory biomarker analysis in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Roswell Park Cancer Institute 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 I/II trial is studying the side effects and best dose of everolimus when given together with sorafenib tosylate and to see how well they work in treating patients with advanced solid tumors and metastatic pancreatic cancer that does not respond to gemcitabine hydrochloride. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sorafenib tosylate, everolimus and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
2 sitesUnited States
Study dates
Aug 2009to Dec 2012
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Phase I only: Histologically or cytologically confirmed solid tumors that are advanced and refractory to or lack life-prolonging treatments; patients with histologically or cytologically confirmed renal cell carcinoma and hepatocellular carcinoma will be eligible
  • Phase II: Histologically or cytologically proven metastatic adenocarcinoma of pancreas that had progressed after one prior gemcitabine containing regimen, or progressed within 6 months of the completion of gemcitabine containing adjuvant regimen
  • Patients must have measurable or assessable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Adequate hematological, renal and liver functions as determined by the following:
  • Absolute neutrophil count (ANC) > 1500 cells/mm^3
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  • Hemoglobin >= 9g/dL
  • Platelets >= 100,000 cells/mm^3
  • Serum creatinine within institutional upper limit of normal (ULN) OR >= 60mll/min for patients with creatinine levels above institutional ULN
  • Bilirubin =< 1.5 x ULN
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 times ULN (< 5 x ULN for patients with abnormal values attributable to liver metastases)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times ULN (< 5 x ULN for patients with abnormal values attributable to liver metastases)
  • International normalized ratio (INR) =< 1.5 (Anticoagulation is allowed if target INR =< 1.5 on a stable dose of warfarin or on a stable dose of low-molecular-weight (LMW) heparin for > 2 weeks at the first dose of study agent)
  • Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND Fasting triglycerides =<2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Ability to understand and willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; men should use adequate birth control for at least three months after the last administration of sorafenib and everolimus

Who cannot join

  • Phase II: Patients in whom histological or cryological diagnosis is not consistent with adenocarcinoma including adenosquamous, islet cell, cystoadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma or lymphoma
  • Phase II: Adenocarcinoma arising from a site other than the pancreas (distal bile duct, ampulla of vater or periampullary duodenum)
  • Prior therapy with approved or investigational agents within 4 weeks prior to the start of treatment plan in this protocol
  • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
  • Any active infections
  • Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
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  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management
  • Cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event >= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Known or suspected allergy to sorafenib, everolimus, other rapamycins (sirolimus, temsirolimus), their excipients, or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Presence of central nervous system or brain metastases
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of first study drug
  • Urine protein:creatinine ratio >=1.0 at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of baseline
  • Inability to comply with study and/or follow-up procedures
  • History of concurrent malignancy or history of a second malignancy within the past 5 years
  • Unable to provide informed consent
  • Concomitant use of any medications or substances that are inhibitors or inducers of CYP3A enzyme, which include but not limited to phenytoin, carbamazepine, barbiturates, rifampin, Phenobarbital or St. Johns Wort
  • Phase II: Prior treatment with mTOR inhibitors (e.g., sirolimus, temsirolimus, everolimus) or Ras-MAPK inhibitors (e.g., sorafenib)
  • Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy (except alopecia)
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus (Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines)
  • Severely impaired lung function as defined as spirometry and diffusing capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air; patients are not required to undergo mandatory respiratory function tests at screening to be eligible unless medically necessary
  • Severe and/or uncontrolled non-malignant liver disease such as cirrhosis or severe hepatic impairment defined as Child-Pugh class C
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception
  • Women of childbearing potential (WOCBP) that have a positive urine or serum pregnancy test within 7 days prior to the start of treatment
  • Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Colorado at Denver Health Sciences Center

    Aurora, Colorado, 80045

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I/II Study of Sorafenib and Everolimus in Patients With Advanced Solid Tumors and Gemcitabine-Refractory Metastatic Pancreatic Cancer

This phase I/II trial is studying the side effects and best dose of everolimus when given together with sorafenib tosylate and to see how well they work in treating patients with advanced solid tumors and metastatic pancreatic cancer that does not respond to gemcitabine hydrochloride. Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Giving sorafenib tosylate together with everolimus may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the 6-month overall survival of patients with previously treated gemcitabine (gemcitabine hydrochloride)-refractory metastatic pancreatic cancer treated with the combination of sorafenib (sorafenib tosylate) and everolimus.

II. To determine the recommended Phase II dose of everolimus when administered in combination with sorafenib in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

  1. To determine the response rate, median survival, time to progression, CA 19.9 decline and toxicity spectrum of the combination in this patient population.

II. To characterize the pharmacokinetic (PK) profiles of sorafenib and everolimus when given in combination.

III. To explore the biomarkers that correlate with response to the study combination in patients previously treated with gemcitabine-refractory metastatic pancreas cancer.

OUTLINE: This is a phase I, dose-escalation study of everolimus, followed by a phase II study.

Patients receive everolimus (PO) once daily and sorafenib tosylate PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for up to 1 year.

Being tested
sorafenib tosylate, everolimus, laboratory biomarker analysis, pharmacogenomic studies, pharmacological study
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given PO

  • everolimusDrug

    Also called 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

    Given PO

  • laboratory biomarker analysisOther

    Correlative study

  • pharmacogenomic studiesOther

    Also called Pharmacogenomic Study

    Correlative study

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative study

Study groups in NCT00981162
Study groupRoleWhat they receive
Treatment (sorafenib tosylate and everolimus)ExperimentalPatients receive everolimus PO once daily and sorafenib tosylate PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: sorafenib tosylate; Drug: everolimus; Other: laboratory biomarker analysis; Other: pharmacogenomic studies; Other: pharmacological study

What is being measured

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

  1. Overall survival (Phase II)

    The estimated distribution of overall survival will be obtained using the product-limit based Kaplan-Meier method. Estimates of quantities such as median survival will be obtained.

    Measured: Time from date of subject enrollment to the date of death due to any cause, assessed up to 6 months

  2. Maximum tolerated dose of everolimus (Phase I)

    Assessed by National Cancer Institute (NCI) CTCAE v3.0.

    Measured: 28 days

Secondary outcomes (5)

  1. Overall response rate (Phase II)

    Will be computed with a corresponding exact 95% confidence interval.

    Measured: Up to 1 year

  2. Differences in biomarkers between responders and non-responders (Phase II)

    Measured: Baseline and days 1 and 15 of course 1

  3. PK parameters (Phase II)

    Will be summarized in each cohort of patients. Comparison of PK parameters among the dose levels will be performed using non-parametric statistical methods for K-independent samples.

    Measured: Baseline and days 1 and 15 of course 1

  4. Correlation of predicted drug concentration or area under the curve (AUC) with biomarker response for each drug and/or in combination (Phase II)

    Measured: Baseline and days 1 and 15 of course 1

  5. Toxicity and adverse events as assessed by NCI CTCAE v3.0

    All toxicities and adverse events in the Phase I and Phase II portions will be summarized with frequencies and descriptive measures.

    Measured: Up to 30 days post-treatment

Timeline

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

  1. First posted22 Sep 2009 (estimated)
  2. Study startAug 2009
  3. Primary completionAug 2011
  4. Study completionDec 2012

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00981162
Sponsor's protocol ID
I 150109
Other IDs
NCI-2009-01326, I 150109
Status last verified
Sep 2022
First submitted
21 Sep 2009
Last updated
13 Sep 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing sorafenib tosylate, everolimus and laboratory biomarker analysis in people with Acinar Cell Adenocarcinoma of the Pancreas and Duct Cell Adenocarcinoma of the Pancreas, run by Roswell Park Cancer Institute 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 17 inclusion and 33 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 13 Sep 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 (Phase II) (time frame: Time from date of subject enrollment to the date of death due to any cause, assessed up to 6 months). 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 NCT00981162.

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 13 Sep 2022.

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