Combination Sunitinib and Gemcitabine in Sarcomatoid and/or Poor-risk Patients With Metastatic Renal Cell Carcinoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00556049
• Collaborator: Pfizer (Industry), Beth Israel Deaconess Medical Center (Other), Dana-Farber Cancer Institute (Other)
• Enrollment: 72
• Locations: 3
• Arm: 1
• Duration (Months): 84
• Patients Per Site: 24
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if the combination of sunitinib and gemcitabine is effective in treating patients with metastatic renal cell carcinoma. The safety of this combination will also be studied. Sunitinib is approved by the FDA for the treatment of renal cell carcinoma. However, some patients' cancers do not respond to treatment or stops responding after initially responding. Gemcitabine is a chemotherapy drug that is approved by the FDA for the treatment of pancreatic cancer and several other cancers. It is not approved for the treatment of renal cell carcinoma. Previous research has suggested that combining gemcitabine with sunitinib may have some effectiveness in treating metastatic renal cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma; Neoplasm Metastases	Drug: Gemcitabine; Drug: Sunitinib	Phase 2

Detailed Description

• Participants will receive study treatment as an outpatient. Study treatment will be given in 3-week cycles.

• Sunitinib will be taken orally once per day for the first two weeks (days 1-14) of each treatment cycle.

• Gemcitabine will be given intravenously at the study clinic on days 1 and 8 of each treatment cycle.

• Before receiving sunitinib and gemcitabine on day 1 of each cycle the following will be performed: physical exam, performance status assessment and blood work. Before receiving gemcitabine on day 8 the following will be performed: physical exam, performance status assessment and blood work. Every 3 cycles a CT scan will be performed to measure the tumor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II, Single Arm Trial of Combination Sunitinib and Gemcitabine in Sarcomatoid and/or Poor-risk Patients With Metastatic Renal Cell Carcinoma
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sunitinib and gemcitabine	Drug: Gemcitabine; Intravenously on days 1 and 8 of each 21-day treatment cycle.; Other Names: Gemzar ; Drug: Sunitinib; Orally on days 1-14 of each 21-day treatment cycle; Other Names: Sutent

Outcome Measures

Primary Outcome Measures

1. To Determine the Overall Response Rate of Combination Therapy With Gemcitabine and Sunitinib in Sarcomatoid and/or Poor-risk mRCC Patients as First Line Therapy. [Until disease progression]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically proven metastatic renal cell carcinoma with any sarcomatoid histology or poor-risk features as defined by having 3 or more of the following characteristics:

• PS > 1, high serum lactate dehydrogenase

• low hemoglobin

• high "corrected" serum calcium

• 2 or more sites of metastatic disease

• time from initial diagnosis to evidence of metastatic disease 12 months or less

• Evidence of unidimensional measurable disease based on RECIST criteria, with at least 1 measurable lesion

• Male or female, 18 years of age or older

• ECOG performance status of 0-2

• Patients with brain metastasis can only be included of they were treated 4 weeks or more prior to enrollment with whole brain radiation and the effects of treatment have resolved

• Resolution of all acute toxic effects of prior therapy, radiotherapy or surgical procedure to NCI CTCAE version 3.0 grade of 1 or less

• Laboratory values as outlined in the protocol

• 2 weeks or more must have elapsed from the time of major surgery or radiation therapy prior to the day of registration

• No anticipated need for major surgical procedure during the course of the study

Exclusion Criteria:

• Prior treatment with sunitinib or gemcitabine

• More than one prior systemic therapy of any kind for renal cell carcinoma

• Uncontrolled high blood pressure

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or symptomatic congestive heart failure

• Ejection fraction < 30%

• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication

• NCT CTCAE grade 3 or higher hemorrhage within 4 weeks of starting treatment

• Significant vascular disease

• Current grade 3 or higher cardiac dysrhythmia or QT prolongation

• Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide

• Pregnancy or breastfeeding or inadequate contraception

• Evidence of bleeding diathesis or coagulopathy

• Serious, non-healing wound, ulcer or bone fracture

• Psychiatric illness/social situation that would limit compliance with study requirements

• Previous diagnosis of concurrent malignancy requiring active systemic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center'	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Massachusetts General Hospital
• Pfizer
• Beth Israel Deaconess Medical Center
• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: M. Dror Michaelson, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dror Michaelson, MD, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00556049
• Other Study ID Numbers: 07-212
• First Posted: Nov 9, 2007
• Last Update Posted: Apr 21, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Dror Michaelson, MD, Assistant Professor of Medicine, Massachusetts General Hospital: mRCC; sunitinib; gemcitabine
• Additional relevant MeSH terms: Carcinoma; Neoplasm Metastasis; Carcinoma, Renal Cell; Gemcitabine; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	Sunitinib and gemcitabine Gemcitabine: Intravenously on days 1 and 8 of each 21-day treatment cycle. Sunitinib: Orally on days 1-14 of each 21-day treatment cycle
Period Title: Overall Study
STARTED	72
COMPLETED	72
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	Sunitinib and gemcitabine Gemcitabine: Intravenously on days 1 and 8 of each 21-day treatment cycle. Sunitinib: Orally on days 1-14 of each 21-day treatment cycle
Overall Participants	72
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	60 83.3%
>=65 years	12 16.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	30 41.7%
Male	42 58.3%
Region of Enrollment (participants) [Number]
United States	72 100%

Outcome Measures

1. Primary Outcome

Title	To Determine the Overall Response Rate of Combination Therapy With Gemcitabine and Sunitinib in Sarcomatoid and/or Poor-risk mRCC Patients as First Line Therapy.
Time Frame	Until disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment
Arm/Group Description	Sunitinib and gemcitabine Gemcitabine: Intravenously on days 1 and 8 of each 21-day treatment cycle. Sunitinib: Orally on days 1-14 of each 21-day treatment cycle
Measure Participants	72
Number [percentage of participants]	25 34.7%

Adverse Events

Arm/Group Title	Neutropenia
Arm/Group Description	Sunitinib and gemcitabine Gemcitabine: Intravenously on days 1 and 8 of each 21-day treatment cycle. Sunitinib: Orally on days 1-14 of each 21-day treatment cycle
All Cause Mortality
	Neutropenia
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Neutropenia
	Affected / at Risk (%)	# Events
Total	20/72 (27.8%)
Blood and lymphatic system disorders
Neutropenia	20/72 (27.8%)
Other (Not Including Serious) Adverse Events
	Neutropenia
	Affected / at Risk (%)	# Events
Total	20/72 (27.8%)
Blood and lymphatic system disorders
Neutropenia	20/72 (27.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.