Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

NCT01198184 | Completed Phase 1

• 5 other identifiers: NCI-2011-025298500CDR0000684714PJC-005U01CA132123
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial is studying the side effects and best dose of giving gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temsirolimus together in treating patients with advanced solid tumors. Gamma-secretase/Notch signalling pathway inhibitor RO4929097 and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose defined as the dose level at which less than or equal to 1 of 6 patients experienced DLT assessed using NCI CTCAE version 4.0

  21 days

• Safety profile assessed using NCI CTCAE version 4.0

  Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Attempts to model associations between pharmacokinetic data with toxicity profiles will be performed primarily using descriptive statistics, however, logistic regression may be used if warranted.

  Up to 4 weeks post-treatment

Secondary Outcomes (3)

• Objective response to treatment assessed using the RECIST criteria 1.1

  Up to 4 weeks post-treatment

• Pharmacokinetic profiles

  Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours

• Pharmacodynamic effects

  Up to 4 weeks post-treatment

Study Arms (1)

Treatment (temsirolimus and RO4929097)

EXPERIMENTAL

Patients receive temsirolimus IV over 30 minutes on day -6 (course 1 only). Patients then receive temsirolimus IV or PO on days 1, 8, and 15 and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO 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.

Drug: temsirolimus; Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

temsirolimus DRUG

Given IV or PO

Also known as: CCI-779, cell cycle inhibitor 779, Torisel

Treatment (temsirolimus and RO4929097)

gamma-secretase/Notch signalling pathway inhibitor RO4929097 DRUG

Given PO

Also known as: R4733, RO4929097

Treatment (temsirolimus and RO4929097)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (temsirolimus and RO4929097)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (temsirolimus and RO4929097)

Eligibility Criteria

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

You may qualify if:

• Meets one of the following sets of criteria:
• Dose-escalation group:
• Histologically and/or cytologically confirmed solid malignancy
• Metastatic or unresectable disease
• Disease for which standard curative or palliative measures do not exist or are no longer effective
• Expansion group:
• Histologically and/or cytologically confirmed endometrial (endometrioid, uterine papillary serious carcinoma, or carcinosarcoma) or renal cell cancer
• Metastatic or unresectable disease
• Disease for which standard curative or palliative measures do not exist or are no longer effective
• Measurable or non-measurable disease
• Measurable disease is defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No known brain metastases
• ECOG performance status (PS) 0-1 (Karnofsky PS 70-100%)
• Life expectancy \> 12 weeks
• Leukocytes ≥ 3,000/mm\^3

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Carcinoma, Renal Cell

Interventions

temsirolimus; Sirolimus; 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)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Amit Oza

  University Health Network-Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 8, 2010
• First Posted: September 9, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2013-10

Locations

CA (2)