Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma in Situ

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

852A

B. H. Gerald Rogers, M. D.

Barrett's esophagus with high-grade dysplasia is a premalignant condition caused by chronic reflux of gastric contents into the esophagus. High-grade dysplasia is the same as carcinoma-in-situ. If untreated, patients with this condition are at high risk for developing cancer of the esophagus. Cancer of the esophagus is a miserable disease that is difficult to treat and about 95% fatal after 5 years. To prevent progession to cancer of the esophagus several interventions are available and they include surgery, Photofrin photodynamic therapy, endoscopic mucosal resection and endoscopic thermal therapy. All of these modalities are uncomfortable, expensive and have associated risks. The oral agent, 852A stimulates the innate immune system in such a way as to eliminate early cancer. A similar dermatologic drug(imiquimod) is approved for treating the premalignant condition, actinic keratosis. If local therapy with imiquimod can eliminate a premalignant lesion in the skin, a similar acting drug should be able to do the same for a premalignant lesion in the lining of the esophagus. This study is designed to test that hypothesis.

This study is to determine if a locally applied immune response modifier will eliminate high grade dysplasia in Barrett's esophagus. Barrett's esophagus is a premalignant condition caused by chronic reflux of gastric contents into the lower esophagus. Present practice is to do a periodic esophagoscopy on patients with Barrett's esophagus and take biopsies in search of dysplasia. If the pathologist reports low grade dysplasia, the patient usually receives more intensive surveillance. If the pathologist reports high grade dysplasia, the patient and his physician are faced with a dilema. High grade dysplasia is carcinoma in situ and there is a strong propensity for such patients to progess to frank carcinoma of the esophagus. Carcinoma of the esophagus is a miserable disease which is difficult to treat and leads to death in about 95% of the cases at 5 years. The present standard for patients with high grade dysplasia is to recommend esophagectomy. Esophagectomy is a major surgical procedure with significant associated morbidity and mortality. Porfimer sodium(Photofrin) photodynamic therapy is effective in eliminating high grade dysplasia in Barrett's esophagus. It has been approved by the FDA but it is not widely utilized because of its complexity and expense. Other modalities such as endoscopic mucosal resection and endoscopic thermal ablation techiques are being studied. Although endoscopic techniques are much safer than surgery, they all are uncomfortable and carry some risk. Many patients with Barrett's esophagus are elderly and most with high grade dysplasia do not live long enough to develop cancer. This fact has made some gastroenterolgists recommend intensive surveillance as an alternative to the above mentioned therapeutic modalities. Intensive surveillance in this setting means endoscopy with biopsies every 3 months with specific therapy recommended only if frank cancer is found. This study is based upon the fact that intensive surveillance is an acceptable way of following these patients. The only difference is an oral agent will be added in hopes of getting rid of high grade dysplasia. If high grade dysplasia could be eliminated by an oral medication it would be a quantum improvement over what we have. The present belief is if high grade dysplasia is eliminated there would be no progression to cancer.

852A is an immune response modifier being developed by 3M Pharmaceuticals. It is thought to exert its therapeutic effect by simulating alpha interferon. 852A is similar to the immune response modifier imiquimod(Aldara). Imiquimod is presently approved by the precancerous dermatological condition, actinic keratosis. It is very effective. Treatment is simply applying 5% imiquimod cream twice weekly to the skin lesion for 16 weeks. It seems reasonable that if an immune response modifier will eliminate precancerous lesions of the skin by local application, the same should be true for precancerous lesions of the esophagus. In this study 852A will be swallowed to see whether it can eliminate high grade dysplasia from the esophagus.

Entrance into the present study would be predicated on the confirmation of high grade dysplasia in Barrett's esophagus. If the prospective subject meets all of the inclusion and exclusion criteria set out in the protocol, endoscopic ultrasound of the esophagus would be done. If endoscopic ultrasound shows no invasion into the submucosa the patient would be asked to sign an informed consent. Once entered into the sudy the subject would be given the study drug twice weekly, 3-4 days apart, for 8 weeks. 852A will be supplied in sterile vials by 3M Pharmaceuticals. Five mg of 852A will be mixed with sterile 5% dextrose in water to give a final volume of 30 ml. The patient will promply swallow the study drug after it is mixed. The subject will then assume a recumbent position for 30 minutes in hopes that the medication will stay in contact with the mucosa of the esophagus long enough to get an effect. All doses of the study medication will be given in the principal investigator's clinic. After the first dose is given that patient will stay in the clinic under observation for 4 hours. Observation includes taking the temperature, pulse, and blood pressure every hour. If there are no adverse effects after the first dose, the observation period after subsequent doses will reduced to one hour. Laboratory tests will be repeated 1,2,4 and 8 weeks after the first dose is given. As set out in the study protocol, if the patient has any significant adverse event or laboratory deviation, the subject would be dropped from the study. Throughout the study the subjects will be treated with a double dose of a proton pump inhibitor to control gastric acid reflux.

After 8 weeks of therapy the study medication will be stopped. Four weeks thereafter and 12 weeks from the beginning, repeat endosocpy with biopsies will be done. If biopsies show no residual high grade dysplasia, the patient will be continued in an intensive surveillance program. Intensive surveillance means endoscopy with biopsies every 3 months for 1 year, then every 6 months for 1 year then yearly for 3 more years. If high grade dysplsia persists after 8 weeks of treatment or cancer is found, the patient would be referred for conventional therapy. Likewise, if high grade dysplsia recurs or cancer is found during the intensive surveillance program, the subject will be referred for conventional therapy.

Pilot Study of Oral 852A for Elimination of High-Grade Dysplasia in Barrett's Esophagus

Rogers, B.H. Gerald, M.D.

B. H. Gerald Rogers, M.D.

Jeffrey Miller, MD

Study 1493-852A is a phase 1 study with the primary objective of determining safety and the highest tolerated dose of an experimental immune response modifier administered intravenously to patients with solid organ tumors not responsive to currently available treatments. The secondary objective of the study is to monitor the tumor response to this form of treatment.

Safety Study of an Immune Response Modifier in Patients With Refractory Solid Organ Tumors

Phase I, Open Label Safety, Pharmacokinetic, and Pharmacodynamic Dose Escalation/De-escalation Study of 852A Administered Intravenously to Subjects With Refractory Solid Organ Tumors

Pfizer

Masonic Cancer Center, University of Minnesota

Jeffrey Miller, M.D.

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Patients receiving at least one dose of 852A.

Subcutaneous injection 0.6 mg/m2 2 times/week/12 weeks, may increase by 0.2 mg/m2 up to 1.2 mg/m2.

Sarah Cooley, MD

The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat certain hematologic malignancies not responding to standard treatment.

852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability

Study of Immune Response Modifier in the Treatment of Hematologic Malignancies

Phase II Study of 852A Administered Subcutaneously in Patients With Hematologic Malignancies Not Responding to Standard Treatment

Stable disease in Non-Hogkin's Lymphoma = disease that does not satisfy complete (complete regression), partial (\> or = 50% reduction) or progressive disease (increase of 25%) by at least a 4-week period. Since Acute Myelogenous Leukemia is not a solid tumor, Complete Response (CR) = \<5% blasts with hematopoietic recovery (absolute neutrophil count \>500) at 4 weeks.

Number of patients who received steroids allowing successful continuation of therapy.

Measurement of peak concentrations of 852A to correlate the side effects of tolerability in patients.

Patients receiving at least 12 doses of 852A.

852A Treatment

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Stable Disease

Partial Response

Progressive Disease

Includes patients receiving at least 12 doses of 852A study drug.

Number of Patients With 852A Response Using Modified Response Evaluation Criteria in Solid Tumors

Number of Patients Who Received Steroids

Analysis not done to sale of agent - unable to perform.

Measure of Immune Activation With Correlative Laboratory Studies

Not able to analysis due to sale of agent - unable to perform.

Peak Concentrations of 852A

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endometrial Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Patients treated with at least one dose - 852A subcutaneous injection.

Patients who received all 24 doses of 852A per protocol.

0.2% 852a subcutaneous injection, 2 times per week for 12 weeks (24 doses) starting at 0.6 mg/m2; subsequent dose escalation for additional courses may be increased by 0.2 mg/m2 not to exceed 1.2 mg/m2.

Melissa A. Geller, MD

The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat metastatic breast, ovarian, endometrial or cervical cancer not responding to standard treatment.

852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability.

Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers

Phase II Study of 852A Administered Subcutaneously in Patients With Metastatic Refractory Breast, Ovarian, Endometrial and Cervical Cancers

Assessment of anti-tumor activity of 852A using Response Evaluation Criteria in Solid Tumors (RECIST) criteria to evaluate tumor response after 24 doses. Complete Response (CR)= disappearance of all target lesions, Partial Response (PR) = at least 30% decrease in sum of longest diameter of target lesions, Progressive Disease (PD) = at least 25% increase in sum of longest diameter of target lesions, Stable Disease = neither PR or PD.

Measures the difference of IL1ra (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures differences in IP-10 (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in MIP-1a (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Macrophage Inflammatory Protein-1 Beta (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Soluble CD40 ligand (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Measures difference in Tumor necrosis factor-alpha (cytokine) values as a means of immune activation pre-treatment and 6 hours post-treatment in patients that received at least one dose of study treatment with 852A.

Melissa Geller, M.D.

Safety (toxicity) is one of the objectives of this study. Only serious adverse events were reported and collected as part of this study.

Patients that received at least one dose of study treatment with 852A (0.6 mg/m\^2 to 1.2 mg/m\^2 dose, 2 times/week for 12 weeks).

Patients Treated With 852A Study Drug

Other Adverse Events that occurred were noted as targeted toxicities and not captured as adverse events.

Complete Response

Participants with ovarian cancer who received all 24 doses of 852A.

Patients With Ovarian Cancer

Includes only patients that received all 24 doses of 852A.

Patients With Tumor Response (Response Evaluation Criteria in Solid Tumors) Who Received All 24 Doses of 852A.

Difference in range values from pre-treatment to post-treatment for cytokine level of IL1ra in patients treated with 852A.

Patients Treated With 852A

One patient did not have value reported at 6 hours after treatment, so cannot be included.

Mean Difference Values for Interleukin 1 Receptor Antagonist (IKL1ra)

Difference in range values from pre-treatment to post-treatment for cytokine level of IP-10 in patients treated with 852A.

One patient did not have a value reported at 6 hours after treatment so cannot be included in analysis.

Mean Difference Values for 10 kDa Interferon-gamma-induced Protein (IP-10)

Difference in range values from pre-treatment to post-treatment for Macrophage Inflammatory Protein-1 Alpha (cytokine) level in patients treated with 852A.

Only 5 patients had a value reported at 6 hours after treatment.

Mean Difference Values for Macrophage Inflammatory Protein-1 Alpha (MIP-1a)

Difference in range values from pre-treatment to post-treatment for cytokine level of MIP-1b in patients treated with 852A.

Two patients did not have recorded values at 6 hours after treatment so cannot be included in analysis.

Mean Difference Values for Macrophage Inflammatory Protein-1 Beta (MIP-1b)

Difference in range values from pre-treatment to post-treatment for cytokine level of sCD40L in patients treated with 852A.

One patient did not have recorded value at 6 hours after treatment and cannot be included in analysis.

Mean Difference Values for Soluble CD40 Ligand (sCD40L)

Difference in range values from pre-treatment to post-treatment for cytokine level of TNF-a in patients treated with 852A.

Only 9 patients had recorded values at 6 hours after treatment and were included in analysis.

Mean Difference Values for Tumor Necrosis Factor-alpha (TNF-a)

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Study 1501-852A is a Phase 1 Study with the objective of determining safety and the highest tolerated dose of an immune response modifier cream directly applied to advanced, inoperable, melanoma skin lesions. The study will also measure blood levels of the drug and examine the potential anti-tumor activity of the cream.

Safety and Efficacy of an Immune Response Modifier to Treat Inoperable Advanced Melanoma Skin Lesions

Director, Clinical Trial Disclosure Group

Pilot study to test the efficacy of 852A administered intravenously up to 3 times per week for 12 weeks in subjects with inoperable metastatic cutaneous melanoma.

Use of 852A in Metastatic Cutaneous Melanoma.

Pilot Phase II, Open Label, Multicenter, Efficacy and Safety Study of 852A Administered Intravenously to Subjects With Unresectable Metastatic Cutaneous Melanoma.

Spots Global Cancer Trial Database for 852a

Every month we try and update this database with for 852a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Study of Oral 852A for Elimination of High-Grade Dysplasia in Barrett's Esophagus	NCT00386594	Barrett Esophag...	852A	18 Years -	Rogers, B.H. Gerald, M.D.
Safety Study of an Immune Response Modifier in Patients With Refractory Solid Organ Tumors	NCT00095160	Neoplasms	852A	18 Years -	Masonic Cancer Center, University of Minnesota
Study of Immune Response Modifier in the Treatment of Hematologic Malignancies	NCT00276159	Acute Lymphobla... Acute Myeloid L... Non-Hodgkin's L... Hodgkin's Lymph... Multiple Myelom... Chronic Lymphoc...	852A	-	Masonic Cancer Center, University of Minnesota
Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers	NCT00319748	Breast Cancer Ovarian Cancer Endometrial Can... Cervical Cancer	852A	18 Years -	Masonic Cancer Center, University of Minnesota
Pilot Study of Oral 852A for Elimination of High-Grade Dysplasia in Barrett's Esophagus	NCT00386594	Barrett Esophag...	852A	18 Years -	Rogers, B.H. Gerald, M.D.
Safety and Efficacy of an Immune Response Modifier to Treat Inoperable Advanced Melanoma Skin Lesions	NCT00091689	Melanoma	852A	18 Years -	Pfizer
Safety and Efficacy of an Immune Response Modifier to Treat Inoperable Advanced Melanoma Skin Lesions	NCT00091689	Melanoma	852A	18 Years -	Pfizer
Use of 852A in Metastatic Cutaneous Melanoma.	NCT00189332	Melanoma Unresectable Me...	852A	18 Years -	Pfizer
Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers	NCT00319748	Breast Cancer Ovarian Cancer Endometrial Can... Cervical Cancer	852A	18 Years -	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for 852a

Every month we try and update this database with for 852a cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for 852a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.