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Clear Cell Renal Cell CarcinomaPhase 2NCT01141569

A Study of RO4929097 in Patients With Advanced Renal Cell Carcinoma That Have Failed Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptor (VEGFR) Therapy

A Phase 2 study testing Gamma-Secretase Inhibitor RO4929097 and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 4 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the activity of RO4929097 in renal cell carcinoma patients that have failed therapy with VEGF/VEGFR directed agents. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Gamma-Secretase Inhibitor RO4929097 and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
4 sitesCanada
Study dates
Jun 2010to Dec 2013
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

Who may be able to join

  • Patients must have histologically or cytologically confirmed predominant clear cell, renal cell carcinoma, NOS, that is recurrent or metastatic
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; scans must be completed within 4 weeks prior to starting study treatment
  • Patients must have had one prior therapy for non-resectable renal cell carcinoma with a VEGF/VEGFR targeted therapy (e.g. sunitinib, sorafenib, other VEGFR tyrosine kinase inhibitor, or bevacizumab)
  • Prior treatment with mTOR inhibitors (Everolimus, Temsirolimus, or rapamycin) for non-resectable disease is permitted
  • Prior immunotherapy is permitted
  • Only one line of prior VEGF/VEGFR is permitted
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  • Life expectancy of greater than 3 months
  • ECOG performance status =< 2 (Karnofsky >= 60%)
  • Patients must have normal organ and marrow function as defined below (within 7days prior to starting study treatment):
  • Hemoglobin >= 90 g/L
  • Absolute granulocyte count >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Total bilirubin =< 1.25 x ULN
  • AST (SGOT)/ALT (SGPT) =< 1.5 x institutional upper limit of normal (=< 5 x ULN for patients with liver metastases)
  • Creatinine =< within institutional normal limits OR creatinine clearance >= mL/min/1.73 m^2 for patients with creatinine levels above institutional (using Cockcroft-Gault formula)
  • Patients must have no serious medical conditions such as myocardial infarction within 6 months prior to entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, psychiatric illness, or any other medical conditions that might be aggravated by treatment or limit compliance
  • Patients must have no active malignancy at any other site
  • Patients must be able to take oral medication and have no evidence of bowel obstruction
  • The effects of RO4929097 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Notch signal pathway inhibitors are known to be teratogenic, if women of childbearing potential do not abstain from sexual activity (documentation that they have been abstinent from sexual activity at least 4 weeks prior to study entry) they must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry; women of childbearing potential be can either be abstinent or use two forms of contraception for the duration of study participation, and be either abstinent or use two forms of contraception for at least 12 months post-treatment; men must use condoms when sexually active with women for the duration of study participation and at least 12 months post-treatment
  • Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately
  • Pregnancy Testing; women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of RO4929097 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of RO4929097; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing RO4929097, the investigator or clinical staff must confirm and document the patient's use of two contraceptive methods or abstinence, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of RO4929097
  • Female patients of childbearing potential are defined as follows:
  • Patients with regular menses
  • Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
  • Women who have had tubal ligation
  • Female patients may be considered to NOT be of childbearing potential for the following reasons:
  • The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy
  • The patient is medically confirmed to be menopausal (no menstrual period) for 24 consecutive months
  • Pre-pubertal females; the parent or guardian of young female patients who have not yet started menstruation should verify that menstruation has not begun; if a young female patient reaches menarche during the study, then she is to be considered as a woman of childbearing potential from that time forward
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients must not have had major surgery, chemotherapy, or radiation therapy within 4 weeks of starting the study treatment (6 weeks for nitrosoureas or mitomycin C); prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that had not been irradiated; patients must have recovered from the toxic effects from any prior therapy to =< grade 1, except alopecia
  • Patients may not be receiving any other investigational agents concurrently
  • Patients with controlled brain metastases (no radiographic progression following radiation and/or surgical treatment and no neurological signs or symptoms) that are clinically and radiologically stable for at least 6 months will be allowed but must NOT be currently taking corticosteroids (e.g. dexamethasone) to control neurologic symptoms of brain metastases
  • Patients with unstable or symptomatic brain metastases, spinal core compression, or carcinomatosis meningitis, or evidence of brain or leptomeningeal disease on screening CT or MRI scan are excluded
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or other agents used in the study
  • Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible
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  • Preclinical studies indicate that RO4929097 is a substrate of CYP3A4 and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; if such patients cannot be switched to alternative medications, they will be ineligible to participate in this study
  • Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow tablets
  • Patients who are serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible
  • Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia other than chronic, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because RO4929097 is a Notch pathway-inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RO4929097, breastfeeding should be discontinued if the mother is treated with RO4929097; these potential risks may also apply to other agents used in this study
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RO4929097; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Cardiovascular: baseline (within 7days prior to starting study treatment) QTc > 450 msec (male) or QTc > 470 msec (female)
  • History of risk factors for QT interval prolongation, including, but not limited to family or personal history of long QT syndrome, recurrent syncope without known etiology or sudden unexpected death
  • History of Torsades de Pointes or other significant cardiac arrhythmias or the need for concomitant meds with known potential to prolong QT interval or antiarrhythmics

Trial locations and contacts

4 sites in 1 country.

Canada4 sites

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • Ottawa Health Research Institute-General Division

    Ottawa, Ontario, K1H 1C4

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase 2 Study of RO4929097 (IND 109291) in Patients With Advanced Renal Cell Carcinoma (RCC, NOS 10038415) That Has Progressed After VEGF/VEGFR Directed Therapy

The purpose of this study is to evaluate the activity of RO4929097 in renal cell carcinoma patients that have failed therapy with VEGF/VEGFR directed agents.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the objective response rate of RO4929097 in patients with advanced kidney cancer and failure of anti-VEGF directed therapy.

SECONDARY OBJECTIVES:

  1. To assess the antitumor activity of RO4929097 through secondary endpoints including: duration of radiologic response, rate of disease stabilizations, rate of tumor control rate (CR+PR+SD), and progression-free \& overall survival rates.

II. To assess the safety and tolerability of single agent RO4929097 in patients with advanced RCC.

III. To explore expression of Notch biomarkers in RCC patients and their potential interaction with RO4929097 response and toxicity.

OUTLINE:

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 orally (PO) on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Being tested
Gamma-Secretase Inhibitor RO4929097, Laboratory Biomarker Analysis
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.

  • Gamma-Secretase Inhibitor RO4929097Drug

    Also called RO4929097

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT01141569
Study groupRoleWhat they receive
Treatment (RO4929097)ExperimentalPatients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Gamma-Secretase Inhibitor RO4929097; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Objective Response Rate (PR + CR) Using RECIST

    Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters

    Measured: Up to 12 months

Secondary outcomes (5)

  1. Time to Progression

    Time to Progression is duration of time from start of treatment to time of progression

    Measured: Up to 12 months

  2. Frequency and Severity of Adverse Events

    Tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest.

    Measured: Up to 12 months

  3. Progression-free Survival Rate

    Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

    Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 12 months

  4. Rate of Disease Stabilizations

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

    Measured: Up to 12 months

  5. Tumor Control Rate (CR + PR + SD)

    Tumor control rate is defined as the sum of objective response rate (CR+PR) and stable disease (SD) rate.

    Measured: Up to 12 months

Timeline

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

  1. First posted10 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionMay 2012
  4. Study completionDec 2013

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 2
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
NCT01141569
Sponsor's protocol ID
NCI-2012-03068
Other IDs
NCI-2012-03068, PHL-077, 8563, N01CM00032
Status last verified
Jan 2017
First submitted
9 Jun 2010
Last updated
10 Mar 2017

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gamma-Secretase Inhibitor RO4929097 and Laboratory Biomarker Analysis in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Carcinoma, run by National Cancer Institute (NCI) at 4 sites in Canada.

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 30 inclusion and 16 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 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. 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 10 Mar 2017). 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?

Objective Response Rate (PR + CR) Using RECIST (time frame: Up to 12 months). 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 NCT01141569.

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 10 Mar 2017.

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