Vaccine Therapy in Treating Patients With Kidney Cancer

Injection of Renal Cell Carcinoma Patients With Human and Mouse Prostate Specific Membrane Antigen (PSMA) DNA: A Phase I Trial to Assess Safety and Immune Response

RATIONALE: Vaccines made from DNA may make the body build an immune response to kill tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with kidney cancer.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Biological: human prostate-specific membrane antigen plasmid DNA vaccine; Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine

Detailed Description

OBJECTIVES:

Primary

• Determine the safety and feasibility of vaccination with human and mouse prostate-specific membrane antigen (PSMA) DNA in patients with renal cell carcinoma.
• Determine the maximum tolerated dose of this regimen in these patients.
• Determine antibody responses to human PSMA in patients treated with this regimen.

Secondary

• Assess antitumor response in patients treated with this regimen.

OUTLINE: This is a randomized, dose-escalation study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive human prostate-specific membrane antigen (PSMA) DNA vaccine intramuscularly (IM) once every 3 weeks for 3 doses (doses 1-3). Patients then receive mouse PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 4-6).
• Arm II: Patients receive mouse PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 1-3). Patients then receive human PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 4-6).

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional booster vaccinations with the second form of PSMA DNA vaccine received (for doses 4-6) every 8 weeks for up to 4 additional doses.

Cohorts of 3-6 patients per arm receive escalating doses of human and mouse PSMA DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma

• Patients with minimal disease burden are eligible provided they meet one or more of the following criteria:

  • Prior nephrectomy and completely resected metastases

  • Favorable-risk group, as defined by all of the following criteria:

    • Karnofsky 80-100%
    • Hemoglobin ≥ 13 g/dL (male) or ≥ 12 g/dL (female)
    • Corrected calcium ≤ 10 mg/dL
    • Prior nephrectomy
    • Serum lactate dehydrogenase ≤ 200 μ/L
  • Prior nephrectomy with metastases confined to lung and/or small volume metastatic disease (< 3 cm) exclusive of bone and liver
• No spinal, epidural, or CNS lesions
• No bone, liver or brain disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• See Disease Characteristics
• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• WBC ≥ 3,500/mm^3
• Hemoglobin ≥ 12.0 g/dL
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin < 2.0 mg/dL
• SGOT < 3.0 times upper limit of normal

Renal

• See Disease Characteristics
• Creatinine ≤ 2.0 mg/dL OR
• Creatinine clearance ≥ 40 mL/min

Cardiovascular

• No clinically significant cardiac disease
• No New York Heart Association class III or IV heart disease

Pulmonary

• No severe debilitating pulmonary disease

Other

• Fertile patients must use effective contraception
• No other active secondary malignancy within the past 5 years except non-melanoma skin cancer
• No infection requiring antibiotic treatment
• No narcotic- or steroid-dependent pain

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy

Endocrine therapy

• At least 4 weeks since prior corticosteroid therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy to only measurable lesion

Surgery

• See Disease Characteristics
• No concurrent surgery

Other

• Recovered from all prior therapy
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: human PSMA; Patients will receive a total of 6 vaccinations via the intramuscular route. Sites of injection should have intact lymphatic drainage. Groups of six patients will be randomized at each dose level, 3 for each arm, to receive either three immunizations with mouse PSMA followed by three immunizations with human PSMA or three immunizations with human PSMA followed by three immunizations with mouse PSMA.	Biological: human prostate-specific membrane antigen plasmid DNA vaccine; Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine
Experimental: mouse PSMA; Patients will receive a total of 6 vaccinations via the intramuscular route. Sites of injection should have intact lymphatic drainage. Groups of six patients will be randomized at each dose level, 3 for each arm, to receive either three immunizations with mouse PSMA followed by three immunizations with human PSMA or three immunizations with human PSMA followed by three immunizations with mouse PSMA.	Biological: human prostate-specific membrane antigen plasmid DNA vaccine; Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety	2 years
feasibility	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
antibody responses	2 years
anti-tumor response	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Susan Slovin, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: November 12, 2004
• First Submitted That Met QC Criteria: November 12, 2004
• First Posted (Estimate): November 15, 2004

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; stage I renal cell cancer; stage III renal cell cancer; stage II renal cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 03-125; MSKCC-03125