Tretinoin Plus Interferon Alfa in Treating Patients With Metastatic Kidney Cancer

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00003656
• Collaborator: (none)
• Enrollment: 26
• Locations: 2
• Arm: 1
• Actual Duration (Months): 112
• Patients Per Site: 13
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Tretinoin may help kidney cancer cells develop into normal cells. Interferon alfa may interfere with the growth of cancer cells.

PURPOSE: Phase II trial to study the effectiveness of liposomal tretinoin plus interferon alfa in treating patients who have metastatic kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Biological: recombinant interferon alfa; Drug: tretinoin liposome	Phase 2

Detailed Description

OBJECTIVES:

• Determine the response in patients with metastatic renal cell carcinoma treated with tretinoin liposome and interferon alfa-2b.

• Determine the toxicity of this regimen in these patients.

• Study retinoic acid receptor expression on tissue obtained from selected patients who have tumor biopsies.

OUTLINE: This is a dose-escalation study of tretinoin liposome with concurrent individual dose escalation of interferon alfa-2b. (Phase I closed to accrual as of 9/24/03.)

Patients receive tretinoin liposome IV over 30 minutes once weekly and interferon alfa-2b subcutaneously on five consecutive days (M-F) for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tretinoin liposome until the maximum tolerated dose (MTD) has been determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined additional patients are accrued and treated at that dose. (Phase I closed to accrual as of 9/24/03.)

During the first 3 weeks of the study, patients receive interferon alfa-2b at weekly dose escalations. After week 3, patients continue at the highest acceptable dose level of interferon alfa-2b for the remainder of the study. (Phase I closed to accrual as of 9/24/03.)

Patients are followed at 30 days after the last treatment.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued into the phase I portion of this study (Phase I closed to accrual as of 9/24/03). A total of 14-25 patients will be accrued into the phase II portion of this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Atragen and Interferon Alfa-2b in Patients With Advanced Renal Cell Carcinoma
• Actual Study Start Date: Jan 1, 1999
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All subjects Weekly ATRA-IV with recombinant interferon alfa	Biological: recombinant interferon alfa; Drug: tretinoin liposome

Outcome Measures

Primary Outcome Measures

1. Best Response as Measured by CT, Bone Scans, and Clinical Progression [After 8 weeks]

2. Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose [In 30 days after the last dose, an average of 1 year.]

Secondary Outcome Measures

1. Change in Retinoic Acid Receptor Expression on Tissue as Measured by Number of Subjects With the Presence of Peripheral Blood Lymphocytes During the First and Fifth Dose [At baseline and 5th week]

2. Duration of Response (Progression-free Survival) as Measured by CT, Bone Scans, and Clinical Progression From Initiation of Therapy Until an Increase of ≥ 25% From the Smallest Sum of All Tumor Measurements Obtained During the Best Response [At 6 months and 12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic renal cell carcinoma

• Bidimensionally measurable disease

• No active brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3

• Platelet count at least 100,000/mm^3

• No coagulation disorders

Hepatic:

• Bilirubin less than 1.5 mg/dL

• SGOT and SGPT less than 112.5 IU/L each or less than 2.5 times upper limit of normal

• No clinically significant hepatic disease, including autoimmune hepatitis

Renal:

• Creatinine less than 2 mg/dL OR

• Creatinine clearance greater than 50 mL/min

• No clinically significant renal disease

Cardiovascular:

• No clinically significant cardiac disease

• No thrombophlebitis

Pulmonary:

• No severe debilitating pulmonary disease

• No pulmonary embolism

Other:

• No history of diabetes mellitus prone to ketoacidosis

• No known hypersensitivity to retinoids or retinoic acid derivatives or to interferon or any component of the injection for this study

• No thyroid abnormalities that hinder maintaining thyroid function at the normal range

• No severe infection

• No severe malnutrition

• No clinically significant retinal abnormalities

• No pre-existing psychiatric condition, especially depression or a history of severe psychiatric disorder

• No other concurrent malignancy except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 effective methods of contraception during and for 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No more than 1 prior biological response modifier therapy or immunotherapy

Chemotherapy:

• No more than 1 prior chemotherapy regimen

Endocrine therapy:

• No concurrent steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No prior retinoid therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
2	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Study Chair: David M. Nanus, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

• Goldberg JS, Vargas M, Rosmarin AS, Milowsky MI, Papanicoloau N, Gudas LJ, Shelton G, Feit K, Petrylak D, Nanus DM. Phase I trial of interferon alpha2b and liposome-encapsulated all-trans retinoic acid in the treatment of patients with advanced renal cell carcinoma. Cancer. 2002 Sep 15;95(6):1220-7.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00003656
• Other Study ID Numbers: 9804003327; NYWCCC-0498-209; NCI-V98-1490
• First Posted: Jan 27, 2003
• Last Update Posted: Mar 18, 2022
• Last Verified: Mar 1, 2022

• Keywords provided by Weill Medical College of Cornell University: stage IV renal cell cancer; recurrent renal cell cancer
• Additional relevant MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell; Interferons; Interferon-alpha; Tretinoin

Study Results

Participant Flow

Recruitment Details	Patients were recruited from between April 2002 and March 2005. Data are only available as a combined Arm/Group based on information contained in the study publication. No additional study data is available despite exhausting all efforts to locate the data.

Arm/Group Title	Phase 1 Group	Phase 2 Group
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
Period Title: Overall Study
STARTED	12	14
COMPLETED	12	13
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Phase 1 Group	Phase 2 Group	Total
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Total of all reporting groups
Overall Participants	12	14	26
Age, Customized (years) [Mean (Inter-Quartile Range) ]
Median age	66.5	61.1	63.6
Sex: Female, Male (Count of Participants)
Female	5 41.7%	4 28.6%	9 34.6%
Male	7 58.3%	10 71.4%	17 65.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Prior nephrectomy (Count of Participants)
Yes prior nephrectomy	12 100%	12 85.7%	24 92.3%
No prior nephrectomy	0 0%	2 14.3%	2 7.7%
Histology (Count of Participants)
Clear cell	7 58.3%	9 64.3%	16 61.5%
Clear cell with sarcomatoid features	1 8.3%	4 28.6%	5 19.2%
Papillary	1 8.3%	0 0%	1 3.8%
Xp11	0 0%	1 7.1%	1 3.8%
Unclassified	3 25%	0 0%	3 11.5%
Number of patients with metastases at the time of diagnosis (Count of Participants)
Count of Participants [Participants]	6 50%	8 57.1%	14 53.8%

Outcome Measures

1. Primary Outcome

Title	Best Response as Measured by CT, Bone Scans, and Clinical Progression
Time Frame	After 8 weeks

Outcome Measure Data

Analysis Population Description

Data are only available as a combined Arm/Group based on information contained in the study publication. No additional study data is available despite exhausting all efforts to locate the data.

Arm/Group Title	Phase 1 Group	Phase 2 Group
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
Measure Participants	12	14
Complete Response	1 8.3%	0 0%
Minor Reponse	0 0%	1 7.1%
Partial Response	1 8.3%	3 21.4%
Stable Disease	5 41.7%	4 28.6%
Disease Progression	5 41.7%	6 42.9%

2. Primary Outcome

Title	Number of Subjects With Toxicity by Clinical Evaluation From First Dose to 30 Days After Last Dose
Time Frame	In 30 days after the last dose, an average of 1 year.

Outcome Measure Data

Analysis Population Description

Data are only available as a combined Arm/Group based on information contained in the study publication. No additional study data is available despite exhausting all efforts to locate the data.

Arm/Group Title	Phase 1 Group	Phase 2 Group
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
Measure Participants	12	14
Fatigue : Grade 1	7 58.3%	8 57.1%
Fatigue : Grade 2	5 41.7%	4 28.6%
Fatigue : Grade 3	0 0%	0 0%
Fatigue : Grade 4	0 0%	0 0%
Skin : Grade 1	1 8.3%	3 21.4%
Skin : Grade 2	0 0%	0 0%
Skin : Grade 3	0 0%	0 0%
Skin : Grade 4	0 0%	0 0%
Xeroderma : Grade 1	11 91.7%	5 35.7%
Xeroderma : Grade 2	0 0%	0 0%
Xeroderma : Grade 3	0 0%	0 0%
Xeroderma : Grade 4	0 0%	0 0%
Constipation : Grade 1	5 41.7%	4 28.6%
Constipation : Grade 2	0 0%	0 0%
Constipation : Grade 3	0 0%	0 0%
Constipation : Grade 4	0 0%	0 0%
Cough : Grade 1	4 33.3%	0 0%
Cough : Grade 2	2 16.7%	0 0%
Cough : Grade 3	0 0%	0 0%
Cough : Grade 4	0 0%	0 0%
Anemia : Grade 1	3 25%	2 14.3%
Anemia : Grade 2	1 8.3%	5 35.7%
Anemia : Grade 3	2 16.7%	0 0%
Anemia : Grade 4	0 0%	0 0%
Anorexia : Grade 1	9 75%	6 42.9%
Anorexia : Grade 2	2 16.7%	2 14.3%
Anorexia : Grade 3	0 0%	0 0%
Anorexia : Grade 4	0 0%	0 0%
Neurologic : Grade 1	8 66.7%	9 64.3%
Neurologic : Grade 2	3 25%	1 7.1%
Neurologic : Grade 3	1 8.3%	0 0%
Neurologic : Grade 4	0 0%	0 0%
Diarrhea : Grade 1	5 41.7%	4 28.6%
Diarrhea : Grade 2	0 0%	0 0%
Diarrhea : Grade 3	0 0%	0 0%
Diarrhea : Grade 4	0 0%	0 0%
Nausea/vomiting : Grade 1	2 16.7%	6 42.9%
Nausea/vomiting : Grade 2	2 16.7%	1 7.1%
Nausea/vomiting : Grade 3	0 0%	0 0%
Nausea/vomiting : Grade 4	0 0%	0 0%
Altered mood : Grade 1	8 66.7%	4 28.6%
Altered mood : Grade 2	0 0%	0 0%
Altered mood : Grade 3	0 0%	0 0%
Altered mood : Grade 4	0 0%	0 0%
Leukopenia : Grade 1	2 16.7%	2 14.3%
Leukopenia : Grade 2	2 16.7%	1 7.1%
Leukopenia : Grade 3	3 25%	0 0%
Leukopenia : Grade 4	0 0%	0 0%
Fever : Grade 1	4 33.3%	5 35.7%
Fever : Grade 2	1 8.3%	0 0%
Fever : Grade 3	0 0%	0 0%
Fever : Grade 4	0 0%	0 0%
Renal : Grade 1	1 8.3%	3 21.4%
Renal : Grade 2	1 8.3%	0 0%
Renal : Grade 3	0 0%	0 0%
Renal : Grade 4	0 0%	0 0%
Liver : Grade 1	1 8.3%	2 14.3%
Liver : Grade 2	0 0%	0 0%
Liver : Grade 3	0 0%	0 0%
Liver : Grade 4	0 0%	0 0%
Thrombocytopenia : Grade 1	2 16.7%	3 21.4%
Thrombocytopenia : Grade 2	0 0%	0 0%
Thrombocytopenia : Grade 3	0 0%	0 0%
Thrombocytopenia : Grade 4	0 0%	0 0%
Infusion reaction : Grade 1	0 0%	0 0%
Infusion reaction : Grade 2	0 0%	1 7.1%
Infusion reaction : Grade 3	0 0%	0 0%
Infusion reaction : Grade 4	0 0%	0 0%
Pulmonary : Grade 1	0 0%	1 7.1%
Pulmonary : Grade 2	0 0%	0 0%
Pulmonary : Grade 3	0 0%	1 7.1%
Pulmonary : Grade 4	0 0%	0 0%
Nasal congestion : Grade 1	0 0%	1 7.1%
Nasal congestion : Grade 2	0 0%	0 0%
Nasal congestion : Grade 3	0 0%	0 0%
Nasal congestion : Grade 4	0 0%	0 0%
Hypotension : Grade 1	0 0%	0 0%
Hypotension : Grade 2	0 0%	1 7.1%
Hypotension : Grade 3	0 0%	0 0%
Hypotension : Grade 4	0 0%	0 0%
Cholesterol/TG : Grade 1	0 0%	1 7.1%
Cholesterol/TG : Grade 2	0 0%	0 0%
Cholesterol/TG : Grade 3	0 0%	0 0%
Cholesterol/TG : Grade 4	0 0%	0 0%
Bone pain : Grade 1	0 0%	1 7.1%
Bone pain : Grade 2	0 0%	0 0%
Bone pain : Grade 3	0 0%	0 0%
Bone pain : Grade 4	0 0%	0 0%
Other pain : Grade 1	0 0%	5 35.7%
Other pain : Grade 2	0 0%	0 0%
Other pain : Grade 3	0 0%	0 0%
Other pain : Grade 4	0 0%	0 0%

3. Secondary Outcome

Title	Change in Retinoic Acid Receptor Expression on Tissue as Measured by Number of Subjects With the Presence of Peripheral Blood Lymphocytes During the First and Fifth Dose
Time Frame	At baseline and 5th week

Outcome Measure Data

Analysis Population Description

Phase 1 portion at the RP2D of 90 mg/m2. 6 patients (12 in phase 1 w 6 at 75 mg/m2 and 6 at 90 mg/m2). This was not completed on the other 14 in phase 2 portion.

Arm/Group Title	All Subjects
Arm/Group Description	Weekly ATRA-IV with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
Measure Participants	6
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Duration of Response (Progression-free Survival) as Measured by CT, Bone Scans, and Clinical Progression From Initiation of Therapy Until an Increase of ≥ 25% From the Smallest Sum of All Tumor Measurements Obtained During the Best Response
Time Frame	At 6 months and 12 months

Outcome Measure Data

Analysis Population Description

Data are only available as a combined Arm/Group based on information contained in the study publication. No additional study data is available despite exhausting all efforts to locate the data.

Arm/Group Title	Phase 1 Group	Phase 2 Group
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome	Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
Measure Participants	12	14
6 month	5 41.7%	7 50%
12 month	4 33.3%	3 21.4%

Adverse Events

Adverse Event Reporting Description	Data are only available as a combined Arm/Group based on information contained in the study publication. No additional study data is available despite exhausting all efforts to locate the data.
Arm/Group Title	Phase 1 Group		Phase 2 Group
Arm/Group Description	Weekly ATRA-IV (with three dose levels: 60, 75, and 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome		Weekly ATRA-IV (dosage of 90 mg/m2) with recombinant interferon alfa recombinant interferon alfa tretinoin liposome
All Cause Mortality
	Phase 1 Group		Phase 2 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)
Serious Adverse Events
	Phase 1 Group		Phase 2 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		0/14 (0%)
Investigations
Leukopenia	1/12 (8.3%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Phase 1 Group		Phase 2 Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/12 (100%)		14/14 (100%)
Blood and lymphatic system disorders
Anemia - Grade 1	3/12 (25%)		2/14 (14.3%)
Anemia - Grade 2	1/12 (8.3%)		5/14 (35.7%)
Anemia - Grade 3	2/12 (16.7%)		0/14 (0%)
Leukopenia - Grade 1	2/12 (16.7%)		2/14 (14.3%)
Leukopenia - Grade 2	2/12 (16.7%)		1/14 (7.1%)
Leukopenia - Grade 3	2/12 (16.7%)		0/14 (0%)
Thrombocytopenia - Grade 1	2/12 (16.7%)		3/14 (21.4%)
Cholesterol/TG - Grade 1	0/12 (0%)		1/14 (7.1%)
Cardiac disorders
Hypotension - Grade 2	0/12 (0%)		1/14 (7.1%)
Gastrointestinal disorders
Constipation - Grade 1	5/12 (41.7%)		4/14 (28.6%)
Diarrhea - Grade 1	5/12 (41.7%)		4/14 (28.6%)
Nausea/Vomiting - Grade 1	2/12 (16.7%)		6/14 (42.9%)
Nausea/Vomiting - Grade 2	2/12 (16.7%)		1/14 (7.1%)
General disorders
Fatigue - Grade 1	7/12 (58.3%)		8/14 (57.1%)
Fatigue - Grade 2	5/12 (41.7%)		4/14 (28.6%)
Infusion Reaction - Grade 2	0/12 (0%)		1/14 (7.1%)
Other Pain - Grade 1	0/12 (0%)		5/14 (35.7%)
Hepatobiliary disorders
Liver - Grade 1	1/12 (8.3%)		2/14 (14.3%)
Immune system disorders
Fever - Grade 1	4/12 (33.3%)		5/14 (35.7%)
Fever - Grade 2	1/12 (8.3%)		0/14 (0%)
Metabolism and nutrition disorders
Anorexia - Grade 1	9/12 (75%)		6/14 (42.9%)
Anorexia - Grade 2	2/12 (16.7%)		2/14 (14.3%)
Musculoskeletal and connective tissue disorders
Bone Pain - Grade 1	0/12 (0%)		1/14 (7.1%)
Nervous system disorders
Neurologic - Grade 1	8/12 (66.7%)		9/14 (64.3%)
Neurologic - Grade 3	1/12 (8.3%)		0/14 (0%)
Neurologic - Grade 2	3/12 (25%)		1/14 (7.1%)
Psychiatric disorders
Altered Mood - Grade 1	8/12 (66.7%)		4/14 (28.6%)
Renal and urinary disorders
Renal - Grade 1	1/12 (8.3%)		3/14 (21.4%)
Renal - Grade 2	1/12 (8.3%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Cough - Grade 1	4/12 (33.3%)		0/14 (0%)
Cough - Grade 2	2/12 (16.7%)		0/14 (0%)
Pulmonary - Grade 1	0/12 (0%)		1/14 (7.1%)
Pulmonary - Grade 3	0/12 (0%)		1/14 (7.1%)
Nasal Congestion - Grade 1	0/12 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Skin - Grade 1	1/12 (8.3%)		3/14 (21.4%)
Xeroderma - Grade 1	11/12 (91.7%)		5/14 (35.7%)

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.