A Phase I Cancer Vaccine Study for Patients With Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

Official title:

A Phase I Vaccine Study With Autologous Dendritic Cells Loaded With Oncofetal Antigen/iLRP in Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00715832
• Other study ID #: QI-Breast Vaccine 1
• Status: Recruiting
• Phase: Phase 1
• First received: July 10, 2008
• Last updated: August 25, 2009
• Start date: May 2008
• Est. completion date: February 2015

Study information

• Verified date: August 2009
• Source: Southern Cancer Center
• Contact: Kelli Wilson
• Phone: 251 442 9452
• Email: kelliwilson[@]quantumimmunologics.com
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study uses a molecule or particle that is found only on cancer cells and is unique to cancer cells, as it is not detected on normal tissue. The molecule is known as "oncofetal antigen" or OFA. Because OFA is unique to cancer, the investigators feel OFA could be used to educate the patients' own defenses to more effectively fight the cancer on her own, he or she is harboring. Although investigators found OFA to be present in large concentrations on all cancers, it was found to be especially abundant in breast cancers. Therefore, the investigators feel that this molecule would be a good target for stimulating patient defenses especially against breast cancer cells. To accomplish this, certain defense cells (immune cells) will be washed out from the patients' blood using a machine to which the patient is connected through two small cannulas placed into veins located in the patients' arms. Those cells will be manipulated in the laboratory with artificially engineered OFA. These "reeducated" cells will be injected into the skin of patients. There will be a series of three skin injections in 4 week intervals. It is hoped that this treatment will convert the patients' defenses to a point that effective anti cancer responses will be induced. Effectiveness of the treatment will be monitored with blood tests and assessment of the size of the cancers.

Description:

The study is an open-label study to assess safety and immune responses to the universal tumor antigen OFA/iLRP. All patients will be immunized with 1 x 107 viable OFA/iLRP-loaded mature, autologous monocyte-derived dendritic cells (DCs). The DC vaccine will be administered intradermally into the proximal medial upper extremity, contralateral to the original site of breast cancer once every month for 3 months. Changes in the tumor will be documented. The patient will remain in the study unless toxicity or adverse side effects require discontinuation following RECIST and CTC guidelines, or if the patient withdraws for any other reason.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: February 2015
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Stage IV histologically proven breast cancer as defined by the AJCC Cancer Staging Manual (6 th. Edition 2003).

• Patients must have completed one prior form of chemo and/or radiation therapy for their disease and have failed to achieve remission.

• There must be no clinical or radiographic signs of active brain metastases (CT of brain), or disease to the brain that is not considered controlled.

• At least 4 weeks must have elapsed since chemotherapy or biological therapy and 2 weeks must have elapsed since radiotherapy

• Female patients must be at least 18 years of age

• Must be ambulatory with a ECOG performance status of <2

• Must have common recall antigen DTH skin reaction >2 mm

• Must have lab values as following ANC > 1.5 x 109/L; platelets > 100 x 109/L, Hb> 9 g/dL, creatinine < 1.8 mg/dL or a creatinine clearance > 35 mL/min; total bilirubin < 2 the upper limit of normal, AST and ALT < 2.5 the upper limit of normal; albumin >2.5 g/L

• If of child bearing potential, must practice a reliable method of contraception at screening and must agree to continue this status until 6 months after receiving the last study vaccine injection. An HCG (pregnancy) test will be done monthly until the 3 vaccinations are complete.

• Signed informed consent (see Appendix A, Clinical Protocol section 25.1) to be obtained according to ICH GCP guidelines before the patient is subjected to any extra diagnostic procedures performed for evaluation of eligibility for the trial.

Exclusion Criteria:

• History of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or cervical cancer stage IB

• Active infection requiring continuous use of antibiotic therapy

• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia

• Autoimmune disease currently treated with steroids

• Adverse reactions to vaccines such as anaphylaxis or other serious reactions, e.g. life-threatening reactions to medicine

• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis,systemic lupus erythematosus, scleroderma, polymyositis dermatomyositis, juvenile onset, insulin dependent diabetes, or a vasculitic syndrome

• Pregnancy or lactation

• Any reason why, in the opinion of the investigator, the patient should not participate

• Patients who have received cytotoxic anti-tumor therapy within 4 weeks prior to vaccination

• Patients with active hepatitis (B, C) or HIV+ individuals

• Patients with more than four different lines of chemotherapy in the metastatic setting (excluding adjuvant chemotherapy).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Biological:
• Dendritic Cell Vaccination
Autologous dendritic dells will be pulsed with human recombinant oncofetal antigen (OFP/iLRP). The vaccine will be injected intradermally

Locations

Country	Name	City	State
United States	Quantum Immunologics	Mobile	Alabama

Sponsors (3)

Lead Sponsor	Collaborator
Southern Cancer Center	Quantum Immunologics, Inc., University of South Alabama

Country where clinical trial is conducted

United States, 

References & Publications (17)

Barsoum AL, Coggin JH Jr. Immunogenicity of a soluble partially purified oncofetal antigen from murine fibrosarcoma in syngeneic mice. J Biol Response Mod. 1989 Dec;8(6):579-92. — View Citation

Barsoum AL, Coggin JH Jr. Isolation and partial characterization of a soluble oncofetal antigen from murine and human amniotic fluids. Int J Cancer. 1991 May 10;48(2):248-52. — View Citation

Coggin JH Jr, Barsoum AL, Rohrer JW. 37 kiloDalton oncofetal antigen protein and immature laminin receptor protein are identical, universal T-cell inducing immunogens on primary rodent and human cancers. Anticancer Res. 1999 Nov-Dec;19(6C):5535-42. — View Citation

Coggin JH Jr, Barsoum AL, Rohrer JW. Tumors express both unique TSTA and crossprotective 44 kDa oncofetal antigen. Immunol Today. 1998 Sep;19(9):405-8. Review. — View Citation

Coggin JH Jr, Rohrer JW, Barsoum AL. True immunogenicity of oncofetal antigen/immature laminin receptor protein. Cancer Res. 2004 Jul 1;64(13):4685; author reply 4685. — View Citation

Coggin JH Jr, Rohrer SD, Hester RD, Barsoum AL, Rashid HU, Gussack GS. 44-kd oncofetal transplantation antigen in rodent and human fetal cells. Implications of recrudescence in human and rodent cancers. Arch Otolaryngol Head Neck Surg. 1993 Nov;119(11):1257-66. — View Citation

Coggin JH Jr. Classification of tumor-associated antigens in rodents and humans. Immunol Today. 1994 May;15(5):246-7. — View Citation

Coggin JH Jr. Embryonic antigens in malignancy and pregnancy: common denominators in immune regulation. Ciba Found Symp. 1983;96:28-54. Review. — View Citation

Coggin JH Jr. Oncofetal antigens. Nature. 1986 Jan 30-Feb 5;319(6052):428. — View Citation

Gussack GS, Rohrer SD, Hester RB, Liu PI, Coggin JH Jr. Human squamous cell carcinoma lines express oncofetal 44-kD polypeptide defined by monoclonal antibody to mouse fetus. Cancer. 1988 Jul 15;62(2):283-90. — View Citation

Höltl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL, Coggin JH Jr, Thurnher M. Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res. 2002 Nov;8(11):3369-76. — View Citation

Payne WJ Jr, Coggin JH Jr. Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization. J Natl Cancer Inst. 1985 Sep;75(3):527-44. — View Citation

Rohrer JW, Barsoum AL, Coggin JH Jr. Identification of oncofetal antigen/immature laminin receptor protein epitopes that activate BALB/c mouse OFA/iLRP-specific effector and regulatory T cell clones. J Immunol. 2006 Mar 1;176(5):2844-56. — View Citation

Rohrer JW, Barsoum AL, Dyess DL, Tucker JA, Coggin JH Jr. Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes. J Immunol. 1999 Jun 1;162(11):6880-92. — View Citation

Rohrer JW, Coggin JH Jr. CD8 T cell clones inhibit antitumor T cell function by secreting IL-10. J Immunol. 1995 Dec 15;155(12):5719-27. — View Citation

Rohrer JW, Culpepper C, Barsoum AL, Coggin JH Jr. Characterization of RFM mouse T lymphocyte anti-oncofetal antigen immunity in apparent tumor-free, long-term survivors of sublethal X-irradiation by limiting dilution T lymphocyte cloning. J Immunol. 1995 Mar 1;154(5):2266-80. — View Citation

Zelle-Rieser C, Barsoum AL, Sallusto F, Ramoner R, Rohrer JW, Höltl L, Bartsch G, Coggin JH JR, Thurnher M. Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma. J Urol. 2001 May;165(5):1705-9. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	toxicity		24 months	Yes
Secondary	Response, Survival, Immunological Monitoring, Time to Disease Progression		24 months	No