Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Everolimus 5mg + Pazopanib 600 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.

Everolimus 5mg + Pazopanib 400 mg once daily for 28 days each cycle Participants were treated until disease progression, unacceptable toxicity or patient withdrawal.

All phase I dose expansion participants received Everolimus 5mg and Pazopanib at the maximum tolerated dose established in the dose finding part of the study.

All phase I participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule or the maximum tolerated dose established in the dose finding part of the study.

pazopanib

everolimus

Mark Pomerantz, MD

This research study is evaluating the combination of pazopanib and everolimus in patients that have a malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or metastatic or locally advanced unresectable kidney cancer. In this research study the investigators are testing the safety of the combination of pazopanib and everolimus and finding the appropriate doses to use for further studies.

This protocol has two parts, Phase I Dose Finding and Phase 1 Expansion. Once the maximum tolerated dose has been identified in the Phase I Dose Finding portion, a Phase I expansion cohort of patients with metastatic or locally advanced unresectable kidney cancer will be enrolled.

This is a Phase I study with multiple arms related to planned dose escalation.

Expanded Phase I Pazopanib and Everolimus in Advanced Solid Tumors and Previously Treated Advanced Urothelial Cancer

An Expanded Phase I Study of Pazopanib and Everolimus in Patients With Advanced Solid Tumors and Previously Treated Advanced Urothelial Cancer

The MTD of Pazopanib in combination with Everolimus 5 mg PO QD was determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.

A DLT was defined as an adverse event (a) with treatment attribution of possible, probable, or definite, and (b) occurs during cycle 1, and (c) meets any of the following criteria: Grade 3 or 4 non-hematologic toxicity excluding: nausea/vomiting controlled with antiemetics, Grade 3 hypertension that resolves to ≤150/90 within 7 days with supportive care, and Grade 3 asymptomatic, clinically insignificant laboratory abnormalities (LDH, alkaline phosphatase due to bone metastases, and asymptomatic hypophosphatemia). Hematologic toxicity: Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with bleeding, Grade 4 neutropenia which persists for \>7 days, Grade 4 neutropenia associated with fever \>38.5C; Hematologic toxicity excluded lymphopenia or anemia of any grade. Missing more than 5 days of planned doses for drug-related intolerable grade 2 toxicity;Toxicity related to therapy severe enough to require a dose-reduction.

The objective response rate (ORR) was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Grade 4 treatment-related toxicity rate is the percentage of participants experiencing at least one treatment-related grade 4 adverse event (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.

Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

Duration of response was calculated as the time from achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment until disease progression. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. For target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.

Beth Israel Deaconess Medical Center

Brigham and Women's Hospital

GlaxoSmithKline

Novartis

Dana-Farber Cancer Institute

Assistant Professor of Medicine, Harvard Medical School

Maximum grade toxicity by type was first calculated. Serious adverse events were defined as events with treatment attribution of possibly, probably, or definitely related and grade 3 or higher per CTCAE v4.0. Other adverse events were defined as grade 1-2 events with treatment attribution of possibly, probably, or definitely related and grades 1-5 with unrelated attribution CTCAE v4.0.

Dose Level 0: Everolimus 5mg + Pazopanib 600 mg

Dose Level -1: Everolimus 5mg + Pazopanib 400 mg

All Phase I Dose Expansion Participants

Total

Age, Continuous

Sex: Female, Male

Asian

White

Race/Ethnicity, Customized

United States

Region of Enrollment

Tumor type

The analysis population is comprised of all enrolled participants.

The phase 1 expansion cohort was terminated early due to weak accrual.

Dr. Mark Pomerantz

All phase I dose finding participants received Everolimus 5mg and Pazopanib according to the established dose escalation schedule.

All Phase I Dose Finding Participants

All phase I dose finding participants who received at least one dose of the study drug were evaluable for MTD.

Maximum Tolerated Dose (MTD) [Phase I Dose Finding]

All phase I dose finding participants who received at least one dose of the study drug were evaluable for DLT.

Dose Limiting Toxicity (DLT) [Phase I Dose Finding]

The analysis population is comprised of all enrolled Phase 1 expansion participants.

Objective Response Rate [Expansion]

Dose Level 0: Everolimus 5mg + Pazopanib 600 mg [Dose Finding]

Dose Level -1: Everolimus 5mg + Pazopanib 400 mg [Dose Finding

All phase I dose finding participants who received at least one dose of the study drug were evaluable for toxicity.

Grade 4 Treatment-Related Toxicity Rate [Dose Finding]

Median Progression-Free Survival [Expansion]

The duration of response is only estimated in the phase 1 expansion participants who achieved objective response on treatment.

Mean Duration of Response [Expansion]

All phase I expansion participants who received at least one dose of the study drug were evaluable for toxicity.

Spots Global Cancer Trial Database for Expanded Phase I Pazopanib and Everolimus in Advanced Solid Tumors and Previously Treated Advanced Urothelial Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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