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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00423865

Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors

A Phase 1 study testing cisplatin, everolimus and gene expression analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, 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

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cisplatin, everolimus and gene expression analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Nov 2006to Sep 2011
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

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of 1 of the following:
  • Advanced solid tumor (part A)
  • Confirmation by core biopsy or fine-needle aspiration allowed
  • Solid tumor (part B)
  • Recurrent or metastatic disease
  • Easily accessible for biopsy
  • Measurable disease
  • No uncontrolled brain or leptomeningeal metastases
  • No requirement for glucocorticoids

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 10 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases are present)
  • Creatinine normal OR creatinine clearance ≥ 55 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
  • No HIV positivity
  • No peripheral neuropathy ≥ grade 2
  • No hypertriglyceridemia ≥ grade 2
  • No impaired gastrointestinal function or gastrointestinal disease that may alter the absorption of everolimus, including any of the following:
  • Ulcerative disease
  • Uncontrolled nausea
  • Vomiting
  • Diarrhea
  • Malabsorption syndrome
  • Small bowel resection
  • No other concurrent severe and/or uncontrolled medical disease that would compromise study participation, including any of the following:
  • Uncontrolled diabetes
  • Unstable angina
  • New York Heart Association class III or IV congestive heart failure

PRIOR CONCURRENT THERAPY:

  • No more than 3 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
  • At least 4 weeks since prior major surgery and recovered
  • At least 4 weeks since prior radiation therapy and recovered
  • At least 4 weeks since prior systemic anticancer therapy and recovered
  • At least 4 weeks since prior and no other concurrent investigational drugs
  • No prior everolimus or other agents specifically targeting mTOR
  • No prior radiation therapy to > 25% of the bone marrow
  • No prior radiation therapy to the whole pelvis and/or brain
  • No concurrent chronic steroid treatment (> 5 mg/day of prednisone)
  • Concurrent low-dose steroid replacement regimens (≤ 5 mg/day of prednisone) allowed
  • No concurrent immunosuppressive agents
  • No other concurrent anticancer agents
  • No concurrent agents known to be strong inhibitors or inducers of isoenzyme CYP3A

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: A Phase I Study of Weekly Low-Dose Cisplatin Plus Escalating Doses of Oral RAD001(Everolimus) for Patients With Advanced Solid Tumors

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also help cisplatin work better by making tumor cells more sensitive to the drug. Giving cisplatin together with everolimus may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cisplatin in treating patients with advanced solid tumors or recurrent or metastatic solid tumors.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the recommended phase II dose of everolimus when administered with low-dose cisplatin in patients with advanced solid tumors.

Secondary

  • Determine the safety and tolerability of this regimen in these patients.
  • Describe the pharmacokinetics of this regimen in patients with advanced solid tumors.
  • Assess the effects of this regimen on p53 and p21 immunohistochemistry assays of pre- and post-treatment tumor biopsies from patients with recurrent or metastatic solid tumors.

OUTLINE: This is a dose-escalation study of everolimus (part A) followed by a biological marker study (part B).

  • Part A (closed to accrual as of 1/2009): Patients receive cisplatin* IV over 30 minutes on days 1, 8, and 15 and oral everolimus* once daily on days 1-21. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 6 patients experience dose-limiting toxicity (DLT) during course 1. The recommended phase II dose is defined as the dose at which 1 of 6 patients experience DLT during course 1.

Blood is drawn periodically on days 1 and 8 of course 1 for pharmacokinetic studies.

  • NOTE: *Patients who have completed 5 courses of treatment and maintain stable disease or better may continue treatment with everolimus alone or in combination with cisplatin
  • Part B: Patients undergo biopsy of the primary tumor, metastatic deposit, or involved lymph node. No more than 14 days later, patients receive everolimus at the recommended phase II dose and cisplatin as in part A.

Patients undergo another tumor biopsy on day 15 of course 1, before receiving chemotherapy. The pre- and post-therapy tissue is examined by immunochemistry and analyzed for p53 and p21 expression.

PROJECTED ACCRUAL: A total of 30 people will be accrued for this study.

Keywords
unspecified adult solid tumor, protocol specific, CISPLATIN, RAD001 (EVEROLIMUS), 06-129

What participants receive

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

  • cisplatinDrug

    cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15)

  • everolimusDrug

    escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle)

  • gene expression analysisGenetic

    Each biopsy specimen will be formalin-fixed and paraffin-embedded for IHC, and analysis of p53 and p21 will follow methods previous reported by our group. The avidin-biotin immunoperoxidase technique will be employed.

  • immunohistochemistry staining methodOther

    After the phase 2 recommended dose is established in the phase I portion of the study (Part A), we plan to enroll an additional 6 patients for pharmacodynamic studies (Part B). Entry into Part B requires the patient have tumor tissue which is easily accessible for research biopsy. The patients will be asked to provide written informed consent for the research biopsies. Patients also will be asked to provide written informed consent to allow the use of their tissue for future research studies. The research biopsies are not mandatory for any patient. Patients who do not consent to the research biopsies or who withdraw consent for the research biopsies may still receive RAD001 + cisplatin in the study

  • laboratory biomarker analysisOther

    Laboratory data (complete blood count, comprehensive metabolic panel including magnesium) regarding adverse events will be collected on each cisplatin treatment day. Additional adverse event data will be collected at regularly scheduled clinic visits at which history and physical are performed by the investigator (Cycle 1 - Days 1, 8, 15, and 21. Cycle 2 - Days 1 and 15. Cycle 3 and beyond - Day 1)

  • pharmacological studyOther

    For patients in Part A, research bloods for pharmacokinetics are drawn on Day 1 and Day 8.

  • biopsyProcedure or surgery

    "Pre-treatment Research Biopsy:" Within 14 days prior to treatment, research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be performed. Baseline labs should be drawn within 14 days of the research biopsy. The biopsy sample will be formalin-fixed and paraffin-embedded for immunohistochemistry. Post-treatment Research Biopsy:" Research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be requested again for Day 15 of Cycle 1, prior to administration of RAD001 and cisplatin on that day.

Study groups in NCT00423865
Study groupRoleWhat they receive
cisplatin & RAD001ExperimentalThis will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors
Receives: Drug: cisplatin; Drug: everolimus; Genetic: gene expression analysis; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: biopsy

What is being measured

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

  1. Recommended phase II dose of everolimus

    Measured: 1 year

Secondary outcomes (2)

  1. Pharmacokinetic profile of cisplatin and everolimus

    Measured: 1 year

  2. Pharmacodynamic profile of cisplatin and everolimus

    Measured: 1 year

Timeline

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

  1. First posted18 Jan 2007 (estimated)
  2. Study startNov 2006
  3. Primary completionSep 2011
  4. Study completionSep 2011

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00423865
Sponsor's protocol ID
MSKCC 06-129
Other IDs
MSKCC-06129
Status last verified
Sep 2012
First submitted
16 Jan 2007
Last updated
25 May 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cisplatin, everolimus and gene expression analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, 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?

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 25 May 2015. 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?

Recommended phase II dose of everolimus (time frame: 1 year). 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 NCT00423865.

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 25 May 2015.

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