A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer.

Cancer Clinical Trial

Official title:

A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer Expressing NY-ESO-1 or LAGE-1.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00199836
• Other study ID #: LUD2002-007
• Status: Completed
• Phase: Phase 1
• Start date: September 3, 2003
• Est. completion date: June 6, 2006

Study information

• Verified date: October 2022
• Source: Ludwig Institute for Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This cancer vaccine research study involves the injection of the NY-ESO-1b peptide along with 2 other agents to help stimulate the immune system. Peptides are small fragments of protein. NY- ESO-1 peptides are normally found in the testis and the placenta. They have also been found on various types of cancer cells. The purpose is to stimulate the immune system to react against the peptides that are found on cancer cells.

Description:

This is a pilot study of patients of HLA-A2 phenotype whose tumor expresses the NY-ESO-1 or LAGE-1 antigen. Patients will receive NY-ESO-1b peptide mixed with 0.5 milliliter (mL) of Montanide® ISA-51 and 1 mg of CpG 7909 given every three weeks for four doses by subcutaneous injection. There will be a three-week follow-up period after the fourth injection making the cycle 13 weeks long. In the absence of toxicity and progressive disease, a second cycle will be offered to patients who have received four vaccinations.

The primary objective is to evaluate the immune response (antibodies, CD8+ T-cells, and DTH) and safety to vaccination with NY-ESO-1b peptide mixed with CpG 7909 and Montanide® in patients with cancer expressing NY-ESO-1 or LAGE-1. The secondary objective is to document tumor responses in patients with evaluable or measurable disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: June 6, 2006
• Est. primary completion date: September 5, 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed metastatic, measurable cancer or resected high risk Stage III/IV; resected Stage II, III, or IV non-small cell lung cancer or esophageal cancer who have declined, failed, or completed standard therapy; tumor expression of NY-ESO-1 or LAGE-1 antigen; HLA-A2 positive; Karnofsky performance status greater than or equal to 60%; hematology and biochemistry laboratory results within the limits normally expected for the patient population; age greater than or equal to 18.

Exclusion Criteria:

• Clinically significant heart disease; other serious illnesses; patients with serious intercurrent illness, requiring hospitalization; patients taking immunosuppressive drugs; autoimmune disease; known HIV positivity; other active malignancy within 1 year prior to entry into the study; participation in chemotherapy, radiation therapy, or any other clinical trial involving another investigational agent within 4 weeks prior to enrollment; pregnancy or breastfeeding; women of childbearing potential: refusal or inability to use effective means of contraception.

Related Conditions & MeSH terms

• Cancer
• Neoplasm

Intervention

Biological:
• NY-ESO-1b peptide plus CpG 7909 and Montanide® ISA-51

Locations

Country	Name	City	State
Germany	Krankenhaus Nordwest	Frankfurt

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig Institute for Cancer Research

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Karbach J, Gnjatic S, Bender A, Neumann A, Weidmann E, Yuan J, Ferrara CA, Hoffmann E, Old LJ, Altorki NK, Jäger E. Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival. Int — View Citation

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline.	Blood samples were obtained at baseline (prior to the first dose), prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1 specific antibodies by an enzyme-linked immunosorbent assay (ELISA). A positive response was a readable optical density at 280 nm.	up to 27 weeks
Primary	Number of Patients With NY-ESO-1 Specific Cellular Immunity as Measured by an Increase in NY-ESO-1b Specific CD8+ T-cells Following Treatment.	Blood samples were obtained at baseline, prior to the second, third and fourth injection and 2 weeks after the fourth injection in both cycles 1 and 2 for the assessment of NY-ESO-1b specific CD8+ T-cells by ELISPOT assays.	up to 27 weeks
Primary	Number of Patients With Delayed-Type Hypersensitivity (DTH) Skin Reactions to NY-ESO-1b Peptide	10 mcg NY-ESO-1b peptide was injected intradermally at a separate site from the vaccination at baseline and after the second and fourth injection of each cycle.; Assessment of DTH reactions as evidenced by redness and induration was performed 48 h after injection.; The number of patients with DTH positive skin reactions was reported at each timepoint.	up to 25 weeks
Primary	Safety as Measured by the Number of Patients With Dose Limiting Toxicities (DLT)	DLT was defined as the following toxicities definitely, probably, or possibly related to the administration of NY-ESO-1b peptide, 100 µg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51: = Grade 2 autoimmune phenomena; Asymptomatic bronchospasm or generalized urticaria; = Grade 3 hematological and non hematological toxicities.	up to 28 weeks
Secondary	Number of Patients With Tumor Responses as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)	Computed tomography (CT) scans were performed at screening, and during weeks 13 and 28. Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): = 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): = 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria. No evidence of disease (NED): no target or non-target lesions at baseline and no new lesions identified on post-baseline scans.	up to 28 weeks