Pancreatic CancerPhase 2NCT00499486
Sirolimus in Treating Patients With Advanced Pancreatic Cancer
A Phase 2 study testing sirolimus in people with Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well sirolimus works in treating patients with advanced pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Jun 2009
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven adenocarcinoma of the pancreas
- Locally-advanced or advanced disease which has progressed after one prior gemcitabine-containing regimen
- Unidimensionally measurable disease (defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan) OR evaluable disease
- Tumor tissue available for IHC assessment OR willingness to undergo a safe biopsy of tumor tissue
- ECOG performance status 0-1
- WBC > 3,500 cells/mm³
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- ANC > 1,500 cells/mm³
- Hemoglobin > 9 g/dL
- Serum creatinine ≤ 2.0 mg/dL
- Bilirubin ≤ 2 mg/dL
- ALT, AST, and alkaline phosphatase ≤ 5 times upper limit of normal
- Triglycerides and total cholesterol < 2 times upper limit of normal
- Not pregnant or nursing
Who cannot join
- Histologic or cytologic diagnosis that is not consistent with adenocarcinoma, including adenosquamous, islet cell, cystadenoma or cystadenocarcinoma, carcinoid, or small or large cell carcinoma or lymphoma
- Adenocarcinoma arising from a site other than the pancreas (e.g., distal common bile duct, ampulla of vater or periampullary duodenum)
- Known brain metastases
- PATIENT CHARACTERISTICS:
- Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy, including immunodeficiency and chronic treatment with immunosuppressors
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
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- Active infections
- History of concurrent malignancy or history of a second malignancy within the past 5 years
- Clinically significant cardiovascular disease, including myocardial infarction (within 12 months prior to randomization), unstable angina, grade II or greater peripheral vascular disease, uncontrolled congestive heart failure, or uncontrolled hypertension (i.e., systolic blood pressure (BP) > 170 mm Hg, diastolic BP > 95 mm Hg)
- PRIOR CONCURRENT THERAPY:
- Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy
- Any previous surgery, excluding minor procedures (e.g., dental work or skin biopsy) within 4 weeks of enrollment
- Participation in an investigational new drug trial within 1 month of starting trial
- Treatment with chemotherapy within 30 days of day 1 treatment
- At least 10 days since prior and no concurrent:
- Cyclosporine
- Diltiazem
- Ketoconazole
- Rifampin
- St. Johns wort
- Grapefruit juice
- Concurrent phenytoin, carbamazepine, barbiturates, or phenobarbital
- No other concurrent investigational or commercial agents
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
Official title: Phase II Clinical, Biological and Pharmacological Study of Rapamycin (Rapamune®, Sirolimus) in Patients With Advanced Pancreatic Cancer
RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well sirolimus works in treating patients with advanced pancreatic cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the proportion of patients with previously treated advanced pancreatic cancer surviving at 6 months after treatment with single agent rapamycin.
- To evaluate the relationship between activation of the PI3/Akt/mTOR/S6K signaling pathway in tumor tissues and rapamycin activity in this patient population.
- To characterize toxicity of rapamycin in this patient population.
Secondary
- To determine the response rate, median time to treatment failure, and median survival of patients with previously treated advanced pancreatic cancer who are treated with single agent rapamycin.
- To characterize the pharmacokinetics of rapamycin in this patient population.
- To explore pharmacogenomic variables that affect rapamycin pharmacokinetics and clinical activity in this patient population.
- To determine the pharmacodynamic effects of rapamycin on S6 kinase activation in PBMC, normal skin, and normal oral mucosa obtained from patients treated with the drug and its relationship with rapamycin pharmacokinetics and clinical effects.
- To explore biomarkers in tumor tissues that might be associated with rapamycin clinical effects.
OUTLINE: Patients receive oral sirolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood, normal skin, and tumor tissue collection at baseline and periodically during study for pharmacological, biological, and genotyping studies. Blood samples are analyzed by LC/MS/MS assay to assess rapamycin pharmacokinetics (PKs) during courses 1 and 2 and to determine baseline CYP3A4 activity. Samples are also analyzed by genotyping studies to assess CYP3A4 polymorphisms. Pharmacodynamic activity of rapamycin is assessed in peripheral blood mononuclear cells isolated from PK blood samples using a kinase assay to measure S6K activity. Tumor tissue is collected from pretreatment tumor samples obtained at the time of diagnosis or surgery or by biopsy from patients for whom pre-study tumor specimens are not available. Patients undergo skin biopsies at baseline and on day 1 of course 2 to obtain samples of normal skin. Patients also undergo oral mucosa smears at baseline and weekly during course 1. Tumor tissue, normal skin, and oral mucosa samples are assessed by IHC staining of S6K and p-S6K and by RT-PCR for cyclin D1 and p27.
- Conditions
- Pancreatic Cancer
- Being tested
- sirolimus
- Keywords
- recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer, adenocarcinoma of the pancreas
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called rapamycin
Treatment with rapamycin will begin on Day 1 at a single flat dose level of 5 mg/day. Rapamycin will be administered continuously without interruption through all cycles in an outpatient setting. Each cycle will last 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Sirolimus 5mg. po QD continously (28 days=cycle) Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With Overall Survival at 6 Months
Measured: 6- month survival rate (6mSR)
Response Rate (Complete, Partial Response and Stable Disease) as Assessed by RECIST
Per Response Evaluation Criteria In Solid Tumors Criteria (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; Progression, a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Response for Stable disease was assessed at 2 months and for complete and partial response at 6 months.
Measured: response at 2 and 6 months
Severity of Adverse Events as Assessed by NCI CTCAE v3.0
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startJan 2005
- Primary completionSep 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 47 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Manuel Hidalgo, MD, PhD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00499486
- Sponsor's protocol ID
- JHOC-J0415, CDR0000549899
- Other IDs
- P30CA006973, JHOC-J0415, JHOC-04-06-16-01
- Status last verified
- Oct 2016
- First submitted
- 10 Jul 2007
- Last updated
- 19 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Garrido-Laguna I, Tan AC, Uson M, Angenendt M, Ma WW, Villaroel MC, Zhao M, Rajeshkumar NV, Jimeno A, Donehower R, Iacobuzio-Donahue C, Barrett M, Rudek MA, Rubio-Viqueira B, Laheru D, Hidalgo M. Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer. Br J Cancer. 2010 Aug 24;103(5):649-55. doi: 10.1038/sj.bjc.6605819. Epub 2010 Jul 27.
PubMed 20664591
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical, Biological and Pharmacological Study of Rapamycin (Rapamune®, Sirolimus) in Patients With Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT00499486
- Acronym / sponsor ID
- JHOC-J0415, CDR0000549899
- Conditions
- Pancreatic Cancer
- Keywords
- recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer, adenocarcinoma of the pancreas
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2005
- Primary completion
- Sep 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 11 Jul 2007 (estimated)
- Results
- Posted 19 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well sirolimus works in treating patients with advanced pancreatic cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the proportion of patients with previously treated advanced pancreatic cancer surviving at 6 months after treatment with single agent rapamycin.
- To evaluate the relationship between activation of the PI3/Akt/mTOR/S6K signaling pathway in tumor tissues and rapamycin activity in this patient population.
- To characterize toxicity of rapamycin in this patient population.
Secondary
- To determine the response rate, median time to treatment failure, and median survival of patients with previously treated advanced pancreatic cancer who are treated with single agent rapamycin.
- To characterize the pharmacokinetics of rapamycin in this patient population.
- To explore pharmacogenomic variables that affect rapamycin pharmacokinetics and clinical activity in this patient population.
- To determine the pharmacodynamic effects of rapamycin on S6 kinase activation in PBMC, normal skin, and normal oral mucosa obtained from patients treated with the drug and its relationship with rapamycin pharmacokinetics and clinical effects.
- To explore biomarkers in tumor tissues that might be associated with rapamycin clinical effects.
OUTLINE: Patients receive oral sirolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood, normal skin, and tumor tissue collection at baseline and periodically during study for pharmacological, biological, and genotyping studies. Blood samples are analyzed by LC/MS/MS assay to assess rapamycin pharmacokinetics (PKs) during courses 1 and 2 and to determine baseline CYP3A4 activity. Samples are also analyzed by genotyping studies to assess CYP3A4 polymorphisms. Pharmacodynamic activity of rapamycin is assessed in peripheral blood mononuclear cells isolated from PK blood samples using a kinase assay to measure S6K activity. Tumor tissue is collected from pretreatment tumor samples obtained at the time of diagnosis or surgery or by biopsy from patients for whom pre-study tumor specimens are not available. Patients undergo skin biopsies at baseline and on day 1 of course 2 to obtain samples of normal skin. Patients also undergo oral mucosa smears at baseline and weekly during course 1. Tumor tissue, normal skin, and oral mucosa samples are assessed by IHC staining of S6K and p-S6K and by RT-PCR for cyclin D1 and p27.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: sirolimusSirolimus 5mg. po QD continously (28 days=cycle) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically proven adenocarcinoma of the pancreas
- Unidimensionally measurable disease (defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan) OR evaluable disease
- Tumor tissue available for IHC assessment OR willingness to undergo a safe biopsy of tumor tissue
- ECOG performance status 0-1
- WBC > 3,500 cells/mm³
Key exclusion criteria (23 listed)
- Histologic or cytologic diagnosis that is not consistent with adenocarcinoma, including adenosquamous, islet cell, cystadenoma or cystadenocarcinoma, carcinoid, or small or large cell carcinoma or lymphoma
- Adenocarcinoma arising from a site other than the pancreas (e.g., distal common bile duct, ampulla of vater or periampullary duodenum)
- Known brain metastases
- Uncontrolled medical conditions that could potentially increase the risk of toxicities or complications of this therapy, including immunodeficiency and chronic treatment with immunosuppressors
- Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimusAlso: rapamycinTreatment with rapamycin will begin on Day 1 at a single flat dose level of 5 mg/day. Rapamycin will be administered continuously without interruption through all cycles in an outpatient setting. Each cycle will last 28 days. | Drug | Sirolimus |
Primary outcome
Percentage of Patients With Overall Survival at 6 Months
Time frame: 6- month survival rate (6mSR)
Response Rate (Complete, Partial Response and Stable Disease) as Assessed by RECIST
Time frame: response at 2 and 6 months
Per Response Evaluation Criteria In Solid Tumors Criteria (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; Progression, a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Response for Stable disease was assessed at 2 months and for complete and partial response at 6 months.
Severity of Adverse Events as Assessed by NCI CTCAE v3.0
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20664591Garrido-Laguna I, Tan AC, Uson M, Angenendt M, Ma WW, Villaroel MC, Zhao M, Rajeshkumar NV, Jimeno A, Donehower R, Iacobuzio-Donahue C, Barrett M, Rudek MA, Rubio-Viqueira B, Laheru D, Hidalgo M. Integrated preclinical and clinical development of mTOR inhibitors in pancreatic cancer. Br J Cancer. 2010 Aug 24;103(5):649-55. doi: 10.1038/sj.bjc.6605819. Epub 2010 Jul 27.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuel Hidalgo, MD, PhD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sirolimus in people with Pancreatic Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site 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 13 inclusion and 23 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 19 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 19 Oct 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?
Percentage of Patients With Overall Survival at 6 Months (time frame: 6- month survival rate (6mSR)). The study lists 3 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 NCT00499486, which also lists 1 linked publication.
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 19 Oct 2016.