RO4929097 in Treating Patients With Recurrent and/or Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

NCT01175343 | Completed Phase 2 Results DMC

• 9 other identifiers: NCI-2012-03069PHL-0798635N01CM00032N01CM00038N01CM00071N01CM62201N01CM62203N01CM62209
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 12

Brief Summary

This phase II trial is studying the side effects and how well RO4929097 works in treating patients with recurrent and/or metastatic epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Four Cycle Progression-free Survival Rate

  Defined as the proportion of the study population that has not had tumor progression (symptomatic, RECIST progression, CA-125 progression) or died at the completion of the cycle four mark. RECIST criteria for progressive disease (PD) in target lesions: \>= 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions is also considered progression. In non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. CA-125 PD is based on the progressive serial elevation of serum CA-125 according to: A) elevated CA-125 pretreatment \& normalization of CA-125 or C) CA-125 in normal range pretreatment: CA-125 \>= 2x ULN on 2 occasions. B) elevated CA-125 pretreatment that never normalizes: CA-125 \>= 2x nadir value on 2 occasions

  84 days (4 courses)

Secondary Outcomes (6)

• Overall Response Rate

  Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years

• CA125 Response Rate (GCIG Criteria)

  Time from start of treatment to time of disease progression or death from any cause, whichever came first, assessed up to 2 years

• Overall Survival

  Up to 2 years

• Frequency and Severity of Adverse Events

  Up to 2 years

• Expression of Notch Biomarkers in Advanced Platinum Resistant Ovarian, Fallopian, and Primary Peritoneal Cancers.

  Up to 2 years

Study Arms (1)

Treatment (RO4929097)

EXPERIMENTAL

Patients receive oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood and tumor tissue samples are collected for correlative studies. Ascitic fluid may also be collected.

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

You may qualify if:

• Patients must have histologically or cytologically confirmed ovarian epithelial carcinoma, fallopian tube carcinoma, or primary peritoneal carcinoma that is recurrent or metastatic; patients must have platinum resistant disease, as defined as treatment free interval less than 6 months post completion of platinum-based chemotherapy
• 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 for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
• OR patients must have evidence of progression based on an elevated CA-125 (defined as a value of \> 2 x ULN documented on two separate determinations made \> 2 weeks apart, with the most recent being completed within 7 days prior to start of study treatment) if the physical exam is normal and maximum lesion diameter on the CT scan is \< 20 mm with conventional techniques or as \< 10 mm with spiral CT scan
• Patients must have completed any prior chemotherapy, radiotherapy or surgery \>= 4 weeks (6 weeks for nitrosoureas or mitomycin C) before study entry
• Prior radiotherapy is allowed provided that there is documented progression (either locally or systemically)
• Patients may have had up to 2 prior lines of chemotherapy for recurrent or metastatic disease
• Toxic effects from prior therapy must have resolved to grade 1 or less except for peripheral neuropathy and alopecia
• Life expectancy of greater than 12 weeks
• ECOG performance status =\< 2 (Karnofsky \>= 60%)
• Patients must have normal organ and marrow function as defined below (within 7 days prior to start of study treatment):
• Hemoglobin \>= 90 g/L
• Leukocytes \>= 3.0 x 10\^9/L
• Absolute neutrophil count \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< 2.5 ULN (institutional upper limit of normal)

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• 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; 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, bowel obstruction, 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 serious or life-threatening birth defects 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 (within 7 days prior to start of study treatment): baseline QTc \> 470 msec (female), QTc \> 450 msec (male)
• 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 torsade de pointes or other significant cardiac arrhythmias or the need for concomitant meds with known potential to prolong QT interval or antiarrhythmics

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (12)

Tower Cancer Research Foundation

Beverly Hills, California, 90211-1850, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Ottawa Hospital-Civic Campus

Ottawa, Ontario, K1Y 4E9, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

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)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Dr. Amit M. Oza
• Organization: Princess Margaret Cancer Centre

amit.oza@uhn.ca

416-946-2818

Study Officials

• Amit Oza

  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: August 3, 2010
• First Posted: August 4, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: August 1, 2015
• Last Updated: May 24, 2017
• Results First Posted: May 24, 2017

Record last verified: 2017-04

Locations

US (6); CA (6)