BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)

NCT01453595 | Terminated Phase 1 Results DMC

• 1 other identifier: 11-080
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Kidney; renal cell carcinoma; BEZ235; 11-080

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Study Arms (1)

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.

Drug: BEZ235

Interventions

BEZ235 DRUG

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

BEZ235

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 27286790 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

dactolisib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Limitations and Caveats

Given the number of toxicities seen and the difficulty with patient retention in the dose escalation portion, the sponsor decided to close the trial.

Results Point of Contact

• Title: Dr. Martin Voss
• Organization: Memorial Sloan Kettering Cancer Center

vossm@mskcc.org

646-422-4631

Study Officials

• Ana Molina, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: October 18, 2011
• Study Start: October 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: February 29, 2016
• Results First Posted: February 29, 2016

Record last verified: 2016-02

Locations

US (1)