Colorectal CancerPhase 2NCT00390364
Everolimus in Treating Patients With Advanced or Metastatic Colorectal Cancer That Did Not Respond to Previous Therapy
A Phase 2 study testing everolimus, antiangiogenesis therapy and biopsy in people with Colorectal Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well everolimus works in treating patients with advanced or metastatic colorectal cancer that did not respond to previous… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- everolimus, antiangiogenesis therapy and biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2006to Oct 2007
- 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
DISEASE CHARACTERISTICS:
- Cytologically or pathologically confirmed colorectal adenocarcinoma
- Advanced or metastatic disease
- Refractory to ≥ 1 line of prior therapy
- Not amenable to potentially curative surgical resection
- Mutations in the PI3K gene in tumor tissue
- Tumor tissue available for genetic testing OR willing to undergo baseline tumor biopsy
- Tumor amenable to sequential biopsies
- Willing to undergo 2 sequential tumor biopsies, and 2 sequential skin biopsies
- Measurable lesion with ≥ 1 diameter ≥ 2 cm by conventional CT scan (1 cm by spiral CT scan) in a nonirradiated area
- No known brain metastases
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 12 weeks
- WBC ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Cholesterol and triglycerides ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus
- No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Hypertension
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would preclude study compliance
- No evidence of bleeding diathesis
- Able to swallow tablets
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- No prior targeted therapy against mTOR
- No other concurrent investigational agents
- No concurrent therapeutic anticoagulation
- Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR or PTT are met.
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy, including chemotherapy, hormonal therapy, immunotherapy, alternative therapy, or radiotherapy
- No concurrent live vaccination
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 Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well everolimus works in treating patients with advanced or metastatic colorectal cancer that did not respond to previous therapy.
Read the detailed description
OBJECTIVES:
- Determine response rate, time to tumor progression, and survival of patients with advanced or metastatic refractory colorectal cancer and mutations in the PI3K gene treated with everolimus.
- Determine the toxicity profile of this drug in these patients.
- Measure the signaling pathways activated in these patients.
- Determine the pharmacodynamic effects of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor biopsies and normal skin biopsies at baseline and after the first course of study treatment. Tumor tissue is examined for biological markers (e.g., epidermal growth factor receptor, ERK, Akt, p70s6k, p27, and Rb protein) by immunohistochemistry; apoptosis quantification by TUNEL assay; Ki-67 quantification and Ki-index; gene expression; and c-fos and p27 expression by reverse-transcriptase polymerase chain reaction.
PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- everolimus, antiangiogenesis therapy, biopsy, diagnostic procedure, gene expression analysis
- Keywords
- adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
antiangiogenesis therapyProcedure or surgery
biopsyProcedure or surgery
diagnostic procedureProcedure or surgery
gene expression analysisProcedure or surgery
immunohistochemistry staining methodProcedure or surgery
laboratory biomarker analysisProcedure or surgery
mutation analysisProcedure or surgery
protein tyrosine kinase inhibitor therapyProcedure or surgery
reverse transcriptase-polymerase chain reactionProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate: The Total Number of Participants With Progression of Disease
To determine response rate and time to tumor progression of patients with colorectal cancer and mutations in the PI3KCA gene who are treated with RAD001. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by CT (or MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesion. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 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 lesion.
The outcome measure will be the total number of subjects who show progression of disease.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionOct 2007
- Study completionOct 2007
Why it stopped: Withdrawn due to low accrual
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.
- Other trials for Colorectal 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
- 1 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
- NCT00390364
- Sponsor's protocol ID
- J05107 CDR0000508071
- Other IDs
- JHOC-J05107, NOVARTIS-JHOC-J05107
- Status last verified
- Oct 2014
- First submitted
- 18 Oct 2006
- Last updated
- 8 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Single Agent RAD001 in Patients With Colon Cancer and Activating Mutations in the PI3KCA Gene
- ClinicalTrials.gov ID
- NCT00390364
- Acronym / sponsor ID
- J05107 CDR0000508071
- Conditions
- Colorectal Cancer
- Keywords
- adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, stage III colon cancer, stage IV colon cancer, recurrent rectal cancer, stage III rectal cancer, stage IV rectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawn due to low accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2006
- Primary completion
- Oct 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 19 Oct 2006 (estimated)
- Results
- Posted 8 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying how well everolimus works in treating patients with advanced or metastatic colorectal cancer that did not respond to previous therapy.
Detailed description
OBJECTIVES:
- Determine response rate, time to tumor progression, and survival of patients with advanced or metastatic refractory colorectal cancer and mutations in the PI3K gene treated with everolimus.
- Determine the toxicity profile of this drug in these patients.
- Measure the signaling pathways activated in these patients.
- Determine the pharmacodynamic effects of this drug in these patients.
OUTLINE: This is an open-label study.
Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor biopsies and normal skin biopsies at baseline and after the first course of study treatment. Tumor tissue is examined for biological markers (e.g., epidermal growth factor receptor, ERK, Akt, p70s6k, p27, and Rb protein) by immunohistochemistry; apoptosis quantification by TUNEL assay; Ki-67 quantification and Ki-index; gene expression; and c-fos and p27 expression by reverse-transcriptase polymerase chain reaction.
PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| everolimus | Drug | – |
| antiangiogenesis therapy | Procedure or surgery | – |
| biopsy | Procedure or surgery | – |
| diagnostic procedure | Procedure or surgery | – |
| gene expression analysis | Procedure or surgery | – |
| immunohistochemistry staining method | Procedure or surgery | – |
| laboratory biomarker analysis | Procedure or surgery | – |
| mutation analysis | Procedure or surgery | – |
| protein tyrosine kinase inhibitor therapy | Procedure or surgery | – |
| reverse transcriptase-polymerase chain reaction | Procedure or surgery | – |
Primary outcome
Response Rate: The Total Number of Participants With Progression of Disease
Time frame: 1 month
To determine response rate and time to tumor progression of patients with colorectal cancer and mutations in the PI3KCA gene who are treated with RAD001. Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions assessed by CT (or MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesion. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 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 lesion. The outcome measure will be the total number of subjects who show progression of disease.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 everolimus, antiangiogenesis therapy and biopsy in people with Colorectal 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?
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: stopped early, as of the sponsor's last update on 8 Oct 2014. 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 8 Oct 2014). 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?
Response Rate: The Total Number of Participants With Progression of Disease (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2014.