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Clear Cell Renal Cell CarcinomaPhase 1/2NCT00112840

CCI-779 and Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney Cancer

A Phase 1/2 study testing CCI-779 and Bevacizumab in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by National Cancer Institute (NCI) 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 CCI-779 and bevacizumab and to see how well they work in treating patients with metastatic or unresectable kidney cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CCI-779 and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
2 sitesUnited States
Study dates
May 2005to 10 Sep 2015
Phase
Phase 1/2
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

Who may be able to join

  • Histologically confirmed metastatic or unresectable renal cell cancer
  • Must have a component of conventional clear cell histology
  • The following histologies are excluded:
  • True papillary
  • Sarcomatoid features without any clear cell component
  • Chromophobe
Show all 62Show fewer
  • Oncocytoma
  • Collecting duct tumors
  • Transitional cell carcinoma
  • Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm in the longest diameter by conventional techniques OR ≥ 1.0 cm by spiral CT scan
  • Tumor tissue (from primary tumor or metastases) available AND patient is willing to donate blood for research studies (phase II only)
  • No CNS metastases by head CT scan or MRI
  • Performance status - ECOG 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • No evidence of bleeding diathesis or coagulopathy
  • No history of clinically significant bleeding or active bleeding
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • AST ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • PT/INR ≤ 1.5
  • Patients on full-dose warfarin or stable-dose low molecular weight heparin must have INR > 1.5 but ≤ 3
  • Creatinine ≤ 1.5 times ULN
  • Urine protein ≤ 1+ by dipstick or urinalysis
  • Urine protein < 1,000 mg on a 24-hour urine collection
  • No cerebrovascular accident within the past 6 months
  • No peripheral vascular disease with claudication on < 1 block
  • No New York Heart Association class II-IV congestive heart failure
  • No angina pectoris requiring nitrate therapy
  • No myocardial infarction within the past 6 months
  • No uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 160 mm Hg and/or diastolic BP ≥ 90 mm Hg despite medication
  • No cardiac arrhythmias
  • No other significant cardiovascular disease
  • No ongoing hemoptysis
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3-4 months after study participation
  • Fasting cholesterol ≤ 350 mg/dL
  • Triglycerides ≤ 1.5 times ULN (may achieve using lipid lowering agents)
  • No known hypersensitivity to recombinant human antibodies
  • No significant traumatic injury within the past 4 weeks
  • No serious or non-healing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
  • No pathological conditions that confer a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • No diabetes
  • No other currently active malignancy except nonmelanoma skin cancer
  • Patients are not considered to have a currently active malignancy if they have completed anticancer therapy AND are considered to be at < 30% risk of relapse
  • No other uncontrolled serious medical or psychiatric condition
  • At least 4 weeks since prior biologic response modifiers for metastatic disease
  • No prior bevacizumab or mTOR inhibitors
  • At least 4 weeks since prior chemotherapy for metastatic disease
  • Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion that has not been irradiated
  • At least 4 weeks since prior and no concurrent radiotherapy
  • Prior nephrectomy allowed
  • More than 4 weeks since prior major surgery or open biopsy
  • More than 1 week since prior core biopsy
  • No concurrent major surgery
  • At least 4 weeks (2 weeks for vascular endothelial growth factor [VEGF] receptor tyrosine kinase inhibitor [RTKI] therapy) since prior and no more than 2 therapies (phase II)
  • One of these therapies must have included a RTKI agent administered for a minimum of 4 weeks
  • Concurrent full-dose warfarin or low molecular weight heparin allowed provided dose is stable AND INR requirements are met
  • Concurrent zoledronate for bone metastases and/or hypercalcemia allowed provided therapy was initiated prior to study entry

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase I/II Trial of CCI-779 and Bevacizumab in Stage IV Renal Cell Carcinoma

This phase I/II trial is studying the side effects and best dose of CCI-779 and bevacizumab and to see how well they work in treating patients with metastatic or unresectable kidney cancer. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving CCI-779 together with bevacizumab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose (MTD) and recommended dosing for the combination of CCI-779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase I) II. To determine the proportion of patients with metastatic renal cell cancer who are progression free at 6 months. (Phase II)

SECONDARY OBJECTIVES:

  1. To determine the toxicity of the combination of CCI 779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase II) II. To determine the clinical response rate of CCI 779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase II) III. To determine the time to progression (TTP), disease free survival, and overall survival of CCI 779 and Bevacizumab in patients with metastatic renal cell cancer. (Phase II)

TERTIARY OBJECTIVES:

  1. To identify predictive molecular markers of response, both at the tumor level and in the plasma/serum level, in an exploratory manner.

II. To correlate blood markers of angiogenesis with clinical activity of the combination of CCI-779 and Bevacizumab.

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study. Patients are stratified according to study phase (I vs II).

Phase I: Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of CCI-779 and bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients receive CCI-779 and bevacizumab as in phase I at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.

Being tested
CCI-779, Bevacizumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • CCI-779Drug

    Also called Temsirolimus, Torisel Rapamycin analog, WAY-130779

    CCI-779 is taken IV on days 1, 8, 15, 22 of a 28-day cycle. Dose level is dependent on phase.

  • BevacizumabDrug

    Bevacizumab is taken IV on Days 1 and 15 of a 28-day cycle. Dose Level determined by phase.

Study groups in NCT00112840
Study groupRoleWhat they receive
CCI-779 and bevacizumabExperimentalPatients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of CCI-779 and bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II patients receive CCI-779 and bevacizumab as in phase I at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.
Receives: Drug: CCI-779; Drug: Bevacizumab

What is being measured

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

  1. Dose-limiting Toxicity (DLT) (Phase I)

    For this protocol, dose limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment in the first four weeks of combination therapy, and meeting the following criteria:

    • Grade 4 Absolute neutrophil count (ANC) for 5+ days.
    • Grade 4 anemia or thrombocytopenia of any duration.
    • Serum Creatinine 2 times baseline or 2x upper limit of normal if baseline levels not normal.
    • Any other non-hematologic grade 3 or higher as per NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0, except fatigue and grade 3 Hypertension that is will be controlled with oral medication.
    • Grade 3 triglycerides will be a DLT for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy.

    The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose where 1 or 0 out of 6 patients experience DLT with the next higher dose.

    Measured: Patients observed a minimum of 4 weeks (one full course). The maximum number of cycles observed was 16 cycles.

  2. Proportion of Progression-free Patients at 6 Months (Phase II)

    Determination of progression will be made according to Response Evaluation Criteria in Solid Tumors (RECIST). A progression (PD) is defined as having at least a 20% increase in the sum of the longest dimension of target lesions taking as reference the smallest sum of the largest dimension recorded at baseline.The proportion of progression-free patients will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the success proportion will be calculated. All patients meeting the eligibility criteria who have signed a consent form and begun treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred.

    Measured: 6 months after study entry

Secondary outcomes (3)

  1. Clinical Best Response Rate of CCI-779 and Bevacizumab in Patients With Metastatic Renal Cell (Phase II)

    The number of participants with clinical tumor response to treatment will be evaluated using the Response Evaluation Criteria In Solid Tumors (RECIST).

    Complete Response (CR): Disappearance of all target lesions

    Partial Response (PR): At least a 30% decrease in the sum of the largest dimension (LD) of target lesions taking as reference the baseline sum LD.

    Measured: Up to 3 years from study registration

  2. Time to Progression (Phase II)

    The time to progression is defined as the time from registration to the time of progression. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. The distribution of time to progression will be estimated using the method of Kaplan-Meier.

    Measured: Up to 3 years from study registration

  3. Overall Survival (Phase I and II)

    The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.

    Measured: Up to 3 years from study registration

Timeline

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

  1. First posted3 Jun 2005 (estimated)
  2. Study startMay 2005
  3. Primary completion9 Aug 2010
  4. Study completion10 Sep 2015

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00112840
Sponsor's protocol ID
NCI-2009-00109
Other IDs
NCI-2009-00109, CDR0000428311, NCI-6986, MC0452, 6986, N01CM62205
Status last verified
Jan 2022
First submitted
2 Jun 2005
Last updated
1 Feb 2022

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CCI-779 and Bevacizumab in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by National Cancer Institute (NCI) 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 62 inclusion and 0 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 1 Feb 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 combined 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.

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 11 Sep 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?

Dose-limiting Toxicity (DLT) (Phase I) (time frame: Patients observed a minimum of 4 weeks (one full course). The maximum number of cycles observed was 16 cycles.). 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 NCT00112840.

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 1 Feb 2022.

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