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Bladder CancerPhase 1NCT01182168

Gemcitabine and Split-Dose Cisplatin Plus Everolimus (RAD001) in Patients With Advanced Solid Tumor Malignancies

A Phase 1 study testing gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001) in people with Bladder Cancer and Renal Pelvis Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site 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

The purpose of this study is to test the safety of gemcitabine and cisplatin plus Everolimus (also called RAD001) at different dose levels. We want to find out what effects, good and/or bad, this treatment has on you and your cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer, Renal Pelvis Cancer, Ureter Cancer
What is being tested?
gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Aug 2010to Mar 2016
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

  • Patients must have advanced urothelial cancer histologically confirmed by MSKCC pathology review.
  • Patients may not have received prior systemic chemotherapy for metastatic disease.
  • Patients may have received prior neoadjuvant or adjuvant systemic chemotherapy provided it was completed ≥ 1 year prior to the diagnosis of metastatic disease.
  • Age ≥ 18 years.
  • Karnofsky Performance Status ≥ 70.
  • Expected survival of at least 3 months.
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  • Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to NCI CTCAE grade ≤ 1.
  • Adequate bone marrow function as shown by:
  • ANC ≥ 1.5x 109/L
  • Platelets ≥ 100 x 109/L
  • Hb >9 g/dL
  • Adequate liver function as shown by:
  • Serum bilirubin ≤ 1.5 x ULN
  • INR ≤ 1.5 (or < 3 on anticoagulants)
  • ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
  • Adequate renal function as shown by:
  • Serum creatinine ≤ 2.0 mg/dL OR
  • Calculated creatinine clearance ≥ 50 mL/min/1.73 m2 using the Jelliffe equation:
  • Calculated creatinine clearance = 98 - 0.8 [age(yrs) - 20] x (0.9 if female) Serum creatinine (mg/dL)
  • Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: If a patient's lipid values exceed either one of these criteria upon screening, the patient can only become eligible after successful initiation of appropriate lipid-lowering medication. After lipid-lowering therapy, patients must meet the same criteria - i.e. a fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN - to be eligible for study treatment.
  • Testing for hepatitis B viral load and serological markers (HBV-DNA, HBsAg, HBsAb, and HBcAb) for the following patients:
  • All patients who currently live in (or have lived in) Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, or Greece
  • Patients with any of the following risk factors:
  • Known or suspected past hepatitis B infection
  • Blood transfusion(s) prior to 1990
  • Current or prior IV drug users
  • Current or prior dialysis
  • Household contact with hepatitis B infected person(s)
  • Current or prior high-risk sexual activity
  • Body piercing or tattoos
  • Mother known to have hepatitis B
  • History suggestive of hepatitis B infection, e.g dark urine, jaundice, or right upper quadrant pain
  • Additional patients at the discretion of the investigator
  • Testing for hepatitis C infection (using quantitative RNA-PCR) for patients with any of the following risk factors:
  • Known or suspected past hepatitis C infection (including patients with past interferon "curative" treatment)
  • Blood transfusion(s) prior to 1990
  • Current or prior IV drug users
  • Household contact of hepatitis C infected person(s)
  • Current or prior high-risk sexual activity
  • Body piercing or tattoos
  • Additional patients at the discretion of the investigator

Who cannot join

  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, tyrosine kinase inhibitors, etc.).
  • Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients who may require major surgery during the course of the study.
  • Prior treatment with any investigational drug within the preceding 4 weeks.
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. Patients receiving these corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with Everolimus. 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.
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
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  • Evidence of another active cancer, except for non-melanoma skin carcinoma, in-situ carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: symptomatic congestive heart failure of New York Heart Association Class III or IV.
  • Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease.
  • Severely impaired lung function as evidenced by:
  • TLC <50% predicted OR
  • FVC <50% predicted OR
  • DLCO <40% predicted
  • Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN.
  • Active (acute or chronic) or uncontrolled severe infections.
  • Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis.
  • A known history of HIV seropositivity.
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patients with an active, bleeding diathesis.
  • Female patients who are pregnant or breast-feeding. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of Everolimus.
  • Adults of reproductive potential who are not using effective birth control methods. Men and women of childbearing potential must be willing to use effective barrier method contraception during the trial and for at least 6 months thereafter. Patients are encouraged to continue barrier method contraception for two years or longer after treatment. Hormonal contraceptives are not acceptable as a sole method of contraception.
  • Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
  • Patients with a known hypersensitivity to Everolimus (RAD001) or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  • Patients with a history of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase I Trial of Gemcitabine and Split-Dose Cisplatin Plus Everolimus (RAD001) in Patients With Advanced Solid Tumor Malignancies

The purpose of this study is to test the safety of gemcitabine and cisplatin plus Everolimus (also called RAD001) at different dose levels. We want to find out what effects, good and/or bad, this treatment has on you and your cancer.

Gemcitabine and cisplatin are standard chemotherapy drugs that are commonly used to treat advanced urothelial cancer. Everolimus is a pill that works by shutting down some of the pathways in cancer cells that make tumors grow. Laboratory studies have shown that Everolimus appears to improve the activity of cisplatin against cancer cells.

Being tested
gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001)
Keywords
CISPLATIN, GEMCITABINE, RAD001 (EVEROLIMUS), 10-106
Medical subject headings
Urinary Bladder Neoplasms, Ureteral Neoplasms

What participants receive

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

  • gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001)Drug

    Patients will receive gemcitabine IV and cisplatin IV on days 1 and 8. Everolimus orally will be administered continuously (one cycle = 21 days). Everolimus will be escalated at the following dose levels: 5mg every-other-day, 5mg daily, and 10mg daily. Patients will receive a total of 6 cycles of gemcitabine and cisplatin in combination with Everolimus unless disease progression or unacceptable toxicity occurs.

Study groups in NCT01182168
Study groupRoleWhat they receive
gemcitabine and cisplatin plus EverolimusExperimentalThis is a single-institution phase I study of gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001) in patients with advanced urothelial cancer.
Receives: Drug: gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001)

What is being measured

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

  1. To establish the dose-limiting toxicity (DLT)

    of Everolimus in combination with gemcitabine and split-dose cisplatin in patients with advanced urothelial cancer.

    Measured: 2 years

Secondary outcomes (8)

  1. To establish the maximum tolerated dose (MTD)

    of Everolimus in combination with gemcitabine and split-dose cisplatin in patients with advanced urothelial cancer.

    Measured: 2 years

  2. To evaluate the response rate

    of gemcitabine and split-dose cisplatin plus Everolimus in patients with advanced urothelial cancer and measurable disease as determined by RECIST.

    Measured: 2 years

  3. To evaluate the time to disease progression

    of gemcitabine and split-dose cisplatin plus Everolimus in patients with advanced urothelial cancer and measurable disease as determined by RECIST.

    Measured: 2 years

  4. To assess activated mTOR pathway markers

    in pre-treatment and post-treatment specimens, when available.

    Measured: 2 years

  5. To evaluate overall survival

    in patients with advanced urothelial cancer treated with gemcitabine and split-dose cisplatin plus Everolimus.

    Measured: 2 years

  6. To assess activated PTEN status

    in pre-treatment and post-treatment specimens, when available.

    Measured: 2 years

  7. To assess activated Akt activation

    in pre-treatment and post-treatment specimens, when available.

    Measured: 2 years

  8. to evaluate markers of DNA repair

    specifically BRCA1 and ERCC1 in pre-treatment and post-treatment specimens, when available.

    Measured: 2 years

Timeline

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

  1. First posted16 Aug 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionMar 2016
  4. Study completionMar 2016

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
NCT01182168
Sponsor's protocol ID
10-106
Status last verified
Mar 2016
First submitted
11 Aug 2010
Last updated
31 Mar 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing gemcitabine and split-dose cisplatin plus escalating doses of continuous Everolimus (RAD001) in people with Bladder Cancer and Renal Pelvis Cancer, run by Memorial Sloan Kettering Cancer Center 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 41 inclusion and 25 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 Mar 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 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?

To establish the dose-limiting toxicity (DLT) (time frame: 2 years). 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 NCT01182168.

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 Mar 2016.

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