Phase II Clinical Trial of Gemcitabine and Doxil® for Metastatic Renal Cell Carcinoma

• Sponsor: University of Pittsburgh (Other)
• Overall Status: Completed
• CT.gov ID: NCT00630409
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 60
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to test the hypothesis that the combination of gemcitabine and doxil will have clinical activity in patients with metastatic renal cell carcinoma.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: Gemcitabine; Drug: Doxil	Phase 2

Detailed Description

Patients with metastatic renal cell carcinoma who have received prior therapy with sorafenib, sunitinib or temsirolimus and have progressive disease may participate in this study if all eligibility criteria are met. Doxil will be administered on day 1 and gemcitabine on day 1 and 8 of a 21 day cycle. Tumor responses will be evaluated by RECIST. Up to six cycles of study treatment may be administered. Cardiac ejection fraction will be monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Trial of Gemcitabine and Doxil® for Metastatic Renal Cell Carcinoma
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment.

Drug: Gemcitabine; 800 mg IV day 1 and 8; Other Names: Gemzar ; Drug: Doxil; 24 mg/m2 every 21 days IV; Other Names: doxorubicin adriamycin

Outcome Measures

Primary Outcome Measures

1. Response Rate [Up to 18 weeks for individual; Up to 40 months for cohort]

   Number of participants that experienced response/total number of participants per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Response was defined as Complete Response (CR), the disappearance of all target lesions; Partial Response (PR), a 30% or greater decrease in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

1. Time to Progression [Up to 40 months]

   Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with renal cell carcinoma who have had disease progression through sorafenib, sunitinib, or temsirolimus (within 6 months of treatment).

• Diagnosis of RCC has been confirmed by pathological or cytological examination of tissue obtained from the primary tumor or a metastatic site.

• Clear cell and non-clear cell histological variants are permitted.

• With the exception of prior gemcitabine or any anthracycline (e.g., doxorubicin, epirubicin, DOXIL), any number of prior therapies with are permitted.

• Prior nephrectomy is permitted but not required for eligibility.

• Patients who have received palliative radiation therapy (XRT) to any area other than the brain (see below) may begin therapy immediately after completion of XRT as long as the irradiated lesion(s) is/are not used for clinical response assessment.

Brain metastases:

• Patients requiring XRT or gamma-knife (or similar) therapy to the brain must wait at least 4 weeks after the completion of irradiation before starting therapy.

• Only patients with either stable or regressing brain metastases after irradiation, as determined by CT or MRI, are eligible for therapy.

• No systemic therapy within 28 days prior to enrollment except as below:

• No sorafenib, sunitinib, temsirolimus therapy within 14 days prior to enrollment.

• Toxicities from prior therapy must have resolved to ≤Grade I.

• Survival: anticipated survival of at least three months.

• Renal function: creatinine ≥ 2.0 mg/dL.

• Patients must have a MUGA scan or 2-D echocardiogram indicating an ejection fraction of ≥50% within 42 days prior to the first dose of study drug. The method used at baseline must be used for later monitoring.

• Prior to each new cycle of therapy: hepatic function: AST, ALT ≥ 3X the upper limit of normal, unless the liver is involved by tumor, in which case the transaminases must be ≥ 5X the upper limit of normal. Total bilirubin must be ≥ 1.5 mg/dL.

• Prior to each new cycle of therapy: bone marrow function: absolute neutrophil count (ANC) ≥ 1,500; platelet count ≥ 100,000; hemoglobin ≥ 10 g/dL.

• Performance status: ECOG 0 or 1.

• Age: ≥ 18 years.

• Signed informed consent must be obtained from participating individuals.

• Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide, or surgical sterilization) during treatment and for three months after completing treatment. If a patient becomes pregnant while on study, the patient will be removed from the study and all drug treatment discontinued.

Exclusion Criteria:

• Patients who have received prior therapy with gemcitabine or an anthracycline drug (e.g., doxorubicin, epirubicin, DOXIL).

• Patients with untreated central nervous system metastases.

• Patients with active bacterial or fungal infections.

• Patients with psychiatric disorders that would interfere with consent, compliance with protocol requirements, or follow-up.

• Patients with a history of prior malignancy other than RCC, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years.

• Patients with any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for the entry into the study.

• Pregnant or lactating women.

• History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin HCL or the component of DOXIL,

• History of cardiac disease with New York Heart Association Class II or greater cardiac function or clinical evidence of congestive heart failure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• University of Pittsburgh

Investigators

• Principal Investigator: Leonard J Appleman, MD, PhD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Leonard Appleman, Assistant Professor of Medicine, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT00630409
• Other Study ID Numbers: 04-033
• First Posted: Mar 7, 2008
• Last Update Posted: Mar 10, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Leonard Appleman, Assistant Professor of Medicine, University of Pittsburgh: Renal cell carcinoma; Kidney Cancer; Gemcitabine; Doxil; Chemotherapy
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Gemcitabine; Doxorubicin

Study Results

Participant Flow

Arm/Group Title	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
Arm/Group Description	Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. Gemcitabine: 800 mg IV day 1 and 8 Doxil: 24 mg/m2 every 21 days IV
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
Arm/Group Description	Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. Gemcitabine: 800 mg IV day 1 and 8 Doxil: 24 mg/m2 every 21 days IV
Overall Participants	5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	5 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Number of participants that experienced response/total number of participants per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Response was defined as Complete Response (CR), the disappearance of all target lesions; Partial Response (PR), a 30% or greater decrease in the sum of the longest diameter of target lesions.
Time Frame	Up to 18 weeks for individual; Up to 40 months for cohort

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
Arm/Group Description	Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. Gemcitabine: 800 mg IV day 1 and 8 Doxil: 24 mg/m2 every 21 days IV
Measure Participants	5
Number [percentage of participants]	0 0%

2. Secondary Outcome

Title	Time to Progression
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

Due to lack of follow-up, objective could not be determined.

Arm/Group Title	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
Arm/Group Description	Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. Gemcitabine: 800 mg IV day 1 and 8 + Doxil: 24 mg/m2 every 21 days IV
Measure Participants	5
Median (95% Confidence Interval) [participants]	NA NaN

Adverse Events

Arm/Group Title	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
Arm/Group Description	Patients will receive 3 cycles of therapy as an outpatient. Each 21-day cycle of therapy will comprise: Gemcitabine: IV on days 1 and 8. Doxil: on day 1. Patients with either responding or stable disease will continue to receive additional 3 cycles of therapy with gemcitabine and Doxil until there is radiological evidence of disease progression or they are unable or unwilling to continue treatment. Gemcitabine: 800 mg IV day 1 and 8 Doxil: 24 mg/m2 every 21 days IV
All Cause Mortality
	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Gemcitabine 800 mg/m^2 + Doxil 24 mg/m^2 (IV)
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Hemoglobin	4/5 (80%)
Gastrointestinal disorders
Constipation	2/5 (40%)
Diarrhea	2/5 (40%)
Heartburn/dyspepsia	1/5 (20%)
Mucositis/stomatitis (clinical exam), Oral cavity	4/5 (80%)
Nausea	4/5 (80%)
Taste alteration (dysgeusia)	1/5 (20%)
Vomiting	1/5 (20%)
General disorders
Fatigue (asthenia, lethargy, malaise)	4/5 (80%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	2/5 (40%)
Rigors/chills	2/5 (40%)
Injection site reaction/extravasation changes	1/5 (20%)
Hepatobiliary disorders
Pain, Liver	1/5 (20%)
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/5 (20%)
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils, Sinus	1/5 (20%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Upper airway NOS	1/5 (20%)
Infection with normal ANC or Grade 1 or 2 neutrophils, Urinary tract NOS	2/5 (40%)
Investigations
Leukocytes (total WBC)	2/5 (40%)
Neutrophils/granulocytes (ANC/AGC)	2/5 (40%)
Platelets	2/5 (40%)
Creatinine	1/5 (20%)
Metabolism and nutrition disorders
Anorexia	2/5 (40%)
Albumin, serum-low (hypoalbuminemia)	1/5 (20%)
Metabolic/Laboratory - Other	1/5 (20%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy), Whole body/generalized	1/5 (20%)
Muscular/skeletal hypoplasia	1/5 (20%)
Musculoskeletal/Soft Tissue - Other	1/5 (20%)
Pain, Back	3/5 (60%)
Pain, Joint	1/5 (20%)
Pain, Muscle	1/5 (20%)
Nervous system disorders
Dizziness	1/5 (20%)
Neurology - Other	2/5 (40%)
Respiratory, thoracic and mediastinal disorders
Pain, Throat/pharynx/larynx	1/5 (20%)
Pulmonary/Upper Respiratory - Other	1/5 (20%)
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)	1/5 (20%)
Rash/desquamation	2/5 (40%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.