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

NCT01141569 | Completed Phase 2 Results

• 4 other identifiers: NCI-2012-03068PHL-0778563N01CM00032
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (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

  Up to 12 months

Secondary Outcomes (5)

• Time to Progression

  Up to 12 months

• Frequency and Severity of Adverse Events

  Up to 12 months

• Progression-free Survival Rate

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

• Rate of Disease Stabilizations

  Up to 12 months

• Tumor Control Rate (CR + PR + SD)

  Up to 12 months

Study Arms (1)

Treatment (RO4929097)

EXPERIMENTAL

Patients 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.

Drug: Gamma-Secretase Inhibitor RO4929097; Other: Laboratory Biomarker Analysis

Interventions

Gamma-Secretase Inhibitor RO4929097 DRUG

Given PO

Also known as: RO4929097

Treatment (RO4929097)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (RO4929097)

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Ottawa Health Research Institute-General Division

Ottawa, Ontario, K1H 1C4, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

2,2-dimethyl-N-(6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-N'-(2,2,3,3,3-pentafluoropropyl)malonamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Christian Kollmannsberger
• Organization: BC Cancer Agency Vancouver Cancer Centre

ckollmannsberger@bccancer.bc.ca

604-877-6000

Study Officials

• Christian Kollmannsberger

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2010
• First Posted: June 10, 2010
• Study Start: June 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: December 1, 2013
• Last Updated: March 10, 2017
• Results First Posted: March 10, 2017

Record last verified: 2017-01

Locations

CA (4)