Renal CancerPhase 1/2NCT01453595
BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)
A Phase 1/2 study testing BEZ235 in people with Renal Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cancer
- What is being tested?
- BEZ235
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Apr 2014
- 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
- Advanced renal cell carcinoma. Advanced disease is defined as unresectable, locally recurrent disease or metastatic disease. This must by confirmed by MSKCC pathology review with the following requirements:
- Phase 1b: Any histologic subtype of RCC.
- Phase 2: clear cell type RCC or predominant clear cell component.
- Patients will be screened for prior systemic therapies:
- Phase 1b: Any prior therapy.
- Phase 2: Progression of disease on at least one prior treatment with an mTOR inhibitor (such as everolimus, temsirolimus, ridaforolimus). Other prior systemic therapies including VEGF directed therapy (e.g. sunitinib, sorafenib, bevacizumab) and immunotherapy (e.g. IL-2, interferon-α) are also permitted. Evidence of unidimensionally measurable disease per RECIST 1.1 (Eisenhauer, Therasse et al. 2009).
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- Resolution of all acute toxic effects of prior systemic treatments, radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, which is not declining during the last 2 weeks.
- 18 years of age or older.
- Adequate organ function as defined by the following criteria:
- Absolute neutrophil count (ANC) ≥1,000/μL
- Platelets ≥100,000/μL
- Hemoglobin ≥9.0 g/dL
- Serum calcium ≤12.0 mg/dL
- Serum creatinine ≤1.5 x upper limit of normal (ULN); if this is exceeded, estimated creatinine clearance must be ≥ 30 ml/min
- Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin of ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN)
- Serum aspartate transaminase (AST) and serum alanine transaminase (ALT)
- ≤3 x ULN (≤5 x ULN in the setting of hepatic metastases)
- INR ≤ 2. (Anticoagulation with warfarin is contraindicated)
- Fasting plasma glucose (FPG) ≤ 140mg/dL
- HgbA1c ≤ 8%
- Fasting serum cholesterol ≤300 mg/dL, fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to undergoing study screening procedures.
- Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Patients who have received prior treatment with a P13K inhibitor (Phase 2 portion only).
- Patients within 28 days post major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) or significant traumatic injury.
- Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed if completed 2 weeks prior to study treatment start).
- Patients who have received chemotherapy, immunotherapy or other investigational agents ≤ 2 weeks prior to study treatment start.
- Patients currently receiving medications known to be inducers or moderate / strong inhibitors of CYP3A4 (see table 9.2 for a list) Patients must discontinue such medications ≥ 7 days prior to initiation of study treatment.
- Patients currently receiving medications with a significant risk to induce Torsades de Pointes
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- Patients who are currently receiving treatment with warfarin sodium (Coumadin®). If treatment is discontinued or switched to an alternate anticoagulant prior to enrollment, INR within ≤48h prior to study initiation has to return to ≤ 2 x ULN.
- Patients receiving chronic treatment with systemic corticosteroids or other immunosuppressive agents (inhaled or topical steroids are allowed)
- Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to enrollment. Patients must not be receiving chronic corticosteroid therapy for CNS metastases.
- Patients who have a history of severe medical conditions or other conditions that could affect their participation in the study such as:
- symptomatic intrinsic lung disease requiring oxygen supplementation at baseline
- uncontrolled hypertension (i.e., SBP>180 mmHg or DBP >100mmHg)
- any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
- liver disease such as cirrhosis or decompensated liver disease.
- Impairment of gastrointestinal function that may impair absorption of BEZ235 (e.g. ulcerative diseases, uncontrolled nausea/vomiting; diarrhea ≥ grade 2; malabsorption syndromes after prior small-bowel resection)
- Immunocompromised patients and/or history of HIV seropositivity
- Patients with prior or current cardiac problems including:
- History of unstable angina pectoris (at any time), symptomatic congestive heart failure (NYHA III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction or cerebrovascular accidents ≤ 6 months prior to first study treatment or history of left ventricular dysfunction
- reduced left ventricular ejection fraction (LVEF) of <50% on screening with echocardiogram or multiple gates acquisition (MUGA) scan
- severe valvulopathies with documented compromise in cardiac function
- Any of the following on screening ECG:
- QTc interval > 480 msec (or family history of congenital QTc prolongation)
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Complete left bundle branch block
- Any conduction abnormality requiring pacemaker
- Symptomatic sinus bradycardia
- Any ventricular arrhythmia except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
- Symptomatic pericarditis
- Documented cardiomyopathy of any cause
- Female patients who are pregnant or breast feeding; pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum βhCG laboratory test (> 5 mIU/mL).
- Patients unwilling or unable to comply with adequate double barrier contraception throughout the trial and for 12 weeks after the last dose of study drug (by both male and female patients). This includes the following considerations:
- Hormonal contraceptives may be affected by cytochrome P450 interactions, and are therefore considered neither indicated nor effective.
- Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper), sponge or spermicide.
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
- Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix.
- Patients who have received attenuated live vaccines within one week of study entry. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
- Known intolerance to the study drug (or any of the excipients), and/or known hypersensitivity to PI3K inhibitor (eg. GDC-0980), and/or known hypersensitivity to rapamycins (eg. Sirolimus, everolimus, temsirolimus) or any of the excipients.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase 1b/2 Study of BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)
This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Older kidney cancer medications (such as temsirolimus [Torisel®] or everolimus [Afinitor®]) typically only block one mechanism in cancer cells, so the investigators think that BEZ235 may work even better against kidney cancer.
The purpose of the first part of this study is to test the safety of giving BEZ235 at different doses. The investigators are trying to find a safe dose of BEZ235 and want to find out what effects, good and/or bad, it has on the patient and the cancer.
- Conditions
- Renal Cancer
- Being tested
- BEZ235
- Keywords
- Kidney, renal cell carcinoma, BEZ235, 11-080
- Medical subject headings
- Kidney Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BEZ235Drug
BEZ235 will be taken orally twice daily starting on Day 1, Cycle 1, self-administration will continue twice daily on a continuous schedule with cycle length defined as 28 days. Increasing dosing levels of BEZ235 will be studied sequentially (beginning with Dose Level 1, BEZ235 400mg by mouth twice daily) as per the treatment noted below.
Cohort-1a BEZ235 300 mg by mouth twice daily Cohort 1 BEZ235 400 mg by mouth twice daily Cohort 2 BEZ235 600 mg by mouth twice daily Cohort 3 BEZ235 800 mg by mouth twice daily
| Study group | Role | What they receive |
|---|---|---|
| BEZ235 | Experimental | This is a single-institution, open label, single-arm Phase 1b/2 trial of BEZ235 in patients with advanced RCC. The study will be conducted in two phases:
Phase 1b: dose-escalation will be performed to determine the maximally tolerated dose (MTD) of twice daily BEZ235 to use in Phase 2 (RP2 dose).
Phase 2: subjects with clear cell who have experienced disease progression on prior first or second-line mTOR targeted therapy will be treated on the MTD of twice daily BEZ235. Receives: Drug: BEZ235 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
In patients with advanced clear cell RCC, progressing after prior first-line or second-line mTOR therapy. The determination of antitumor efficacy will be based on objective tumor assessments made according to the RECIST1.1.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Given the number of toxicities seen and the difficulty with patient retention in the dose escalation portion, the sponsor decided to close the trial.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Ana Molina, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01453595
- Sponsor's protocol ID
- 11-080
- Status last verified
- Feb 2016
- First submitted
- 13 Oct 2011
- Last updated
- 29 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Carlo MI, Molina AM, Lakhman Y, Patil S, Woo K, DeLuca J, Lee CH, Hsieh JJ, Feldman DR, Motzer RJ, Voss MH. A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma. Oncologist. 2016 Jul;21(7):787-8. doi: 10.1634/theoncologist.2016-0145. Epub 2016 Jun 10.
PubMed 27286790
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT01453595
- Acronym / sponsor ID
- 11-080
- Conditions
- Renal Cancer
- Keywords
- Kidney, renal cell carcinoma, BEZ235, 11-080
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Given the number of toxicities seen and the difficulty with patient retention in the dose escalation portion, the sponsor decided to close the trial.
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Oct 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 18 Oct 2011 (estimated)
- Results
- Posted 29 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Older kidney cancer medications (such as temsirolimus [Torisel®] or everolimus [Afinitor®]) typically only block one mechanism in cancer cells, so the investigators think that BEZ235 may work even better against kidney cancer.
The purpose of the first part of this study is to test the safety of giving BEZ235 at different doses. The investigators are trying to find a safe dose of BEZ235 and want to find out what effects, good and/or bad, it has on the patient and the cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BEZ235 | Experimental | Drug: BEZ235This is a single-institution, open label, single-arm Phase 1b/2 trial of BEZ235 in patients with advanced RCC. The study will be conducted in two phases: Phase 1b: dose-escalation will be performed to determine the maximally tolerated dose (MTD) of twice daily BEZ235 to use in Phase 2 (RP2 dose). Phase 2: subjects with clear cell who have experienced disease progression on prior first or second-line mTOR targeted therapy will be treated on the MTD of twice daily BEZ235. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Advanced renal cell carcinoma. Advanced disease is defined as unresectable, locally recurrent disease or metastatic disease. This must by confirmed by MSKCC pathology review with the following requirements:
- Phase 1b: Any histologic subtype of RCC.
- Phase 2: clear cell type RCC or predominant clear cell component.
- Phase 1b: Any prior therapy.
- Phase 2: Progression of disease on at least one prior treatment with an mTOR inhibitor (such as everolimus, temsirolimus, ridaforolimus). Other prior systemic therapies including VEGF directed therapy (e.g. sunitinib, sorafenib, bevacizumab) and immunotherapy (e.g. IL-2, interferon-α) are also permitted. Evidence of unidimensionally measurable disease per RECIST 1.1 (Eisenhauer, Therasse et al. 2009).
Key exclusion criteria (38 listed)
- Patients who have received prior treatment with a P13K inhibitor (Phase 2 portion only).
- Patients within 28 days post major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic) or significant traumatic injury.
- Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed if completed 2 weeks prior to study treatment start).
- Patients who have received chemotherapy, immunotherapy or other investigational agents ≤ 2 weeks prior to study treatment start.
- Patients currently receiving medications known to be inducers or moderate / strong inhibitors of CYP3A4 (see table 9.2 for a list) Patients must discontinue such medications ≥ 7 days prior to initiation of study treatment.
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 |
|---|---|---|
| BEZ235BEZ235 will be taken orally twice daily starting on Day 1, Cycle 1, self-administration will continue twice daily on a continuous schedule with cycle length defined as 28 days. Increasing dosing levels of BEZ235 will be studied sequentially (beginning with Dose Level 1, BEZ235 400mg by mouth twice daily) as per the treatment noted below. Cohort-1a BEZ235 300 mg by mouth twice daily Cohort 1 BEZ235 400 mg by mouth twice daily Cohort 2 BEZ235 600 mg by mouth twice daily Cohort 3 BEZ235 800 mg by mouth twice daily | Drug | BEZ235 |
Primary outcome
Objective Response Rate (ORR)
Time frame: 1 year
In patients with advanced clear cell RCC, progressing after prior first-line or second-line mTOR therapy. The determination of antitumor efficacy will be based on objective tumor assessments made according to the RECIST1.1.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27286790Carlo MI, Molina AM, Lakhman Y, Patil S, Woo K, DeLuca J, Lee CH, Hsieh JJ, Feldman DR, Motzer RJ, Voss MH. A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma. Oncologist. 2016 Jul;21(7):787-8. doi: 10.1634/theoncologist.2016-0145. Epub 2016 Jun 10.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
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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.
Ana Molina, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BEZ235 in people with Renal 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 23 inclusion and 38 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: stopped early, as of the sponsor's last update on 29 Feb 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 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 29 Feb 2016). 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 (ORR) (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 NCT01453595, which also lists 1 linked publication.
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 29 Feb 2016.