Solid Tumors Clinical Trial
Official title:
A PHASE I, OPEN LABEL, DOSE-ESCALATION TRIAL EVALUATING THE SAFETY AND TOLERABILITY OF EF-022 (MODIFIED VITAMIN D BINDING PROTEIN MACROPHAGE ACTIVATOR) IN SUBJECTS WITH ADVANCED SOLID MALIGNANCIES
Verified date | June 2017 |
Source | Efranat Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Activated macrophages, present in excess during natural inflammatory responses, bear the
potential to kill and eradicate cancer cells. Macrophage activation has been demonstrated to
require the serum-borne vitamin D binding protein (known as Gc protein), as well as B and T
lymphocytes. However, in various cancer patients the Gc protein is deglycosylated by serum
α-N-acetyl galactosaminidase (Nagalase) secreted from cancer cells. This deglycosylated Gc
protein, lacking the N-acetylgalactosamine monosaccharide, cannot be converted to its form
of Macrophage Activating Factor, leading to immunosuppression rather than Macrophage
activation against cancer cells.
Efranat has developed cancer immunotherapy based on Macrophage Activating Factor produced
from natural Gc protein extracted from FDA approved healthy human plasma.
In this phase I study, the treatment is given as Intramuscular, once-weekly injection of
EF-022, for two courses, while each course is comprised of 4 injections.
The investigational treatment is expected to enhance immune response, thereby, improve
patient's well being, quality of life and disease control.
Primary objectives:
1. To determine the safety and tolerability of EF-022 and to define the maximal tolerated
dose (MTD) for potential administration.
2. To identify the Dose Limiting Toxicity (DLT) of EF-022.
Secondary objectives:
1. To determine the 'Recommended Phase 2 Dose' (RP2D) based on MTD data, immunological and
pharmacodynamics markers
2. To explore preliminary efficacy of EF-022 in advanced solid tumors according to the
'Response Evaluation Criteria in the modified Solid Tumors' (RECIST 1.1) and blood
levels of tumor-related markers known to reflect tumor burden.
Exploratory objectives:
1. To assess levels of immune-related factors in peripheral blood (determined by FACS
analysis), reflecting induced immunological activities, including but not limited to,
natural killer (NK), monocytes (M1 and M2) and T cell subpopulations (effector vs
regulatory, CD4+ and CD8+ cells), B cells (CD20), myeloid and dendritic cells etc.
2. To assess the change in serum levels of protein biomarkers in the blood.
3. To immunohistochemically assess and compare tumor derived tissue samples Pre and post
treatment. To analyze the infiltration of different population of cells into the tumor
bed.
Status | Completed |
Enrollment | 24 |
Est. completion date | May 2017 |
Est. primary completion date | May 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility |
Inclusion Criteria: 1. Patients diagnosed with inoperable, recurrent or metastatic tumor, deemed incurable, and who have either failed to respond to standard therapy or for whom no standard therapy is available or refuse to receive standard therapies or in case of SCC, the investigator decides that delay of the standard therapy does not have any risk for the patient. 2. Histologically or cytological-confirmed diagnosis of solid tumor on file. For the expanded cohort only the following immunological tumors will be recruited: epithelial ovarian cancer, cervical carcinoma, head & neck cancer, melanoma, kidney cancer (RCC), gastric cancer, lung cancer (SCLC or NSCLC), sarcoma, bladder cancer or squamous cell carcinoma (SCC) of the skin. 3. Measurable disease (i.e., present with at least one measurable lesion per modified RECIST, version 1.1). 4. Age: 18-80 years. 5. BMI: 18-36. 6. ECOG Performance Status 0 or 1. 7. Estimated life expectancy of at least 4 months. 8. Off prior chemotherapy, radiation therapy with curative intent, hormonal therapy, immunotherapy, biological therapies (excluded checkpoint inhibitors and Erbitux), immunosuppressive therapy [e.g., cyclosporine, humera, prograf, etc.] or immunomodulators [e.g., thalidomide, revlimid, etc.] for at least 4 weeks. Hormonal treatment is not allowed ONLY if given as an anti-cancer therapy. In any case the sponsor should be consulted prior to final decision. Prior treatment with checkpoint inhibitors (such as anti PD-1, anti PDL-1), and/or Erbitux, and/or palliative irradiation, does not require any wash out period before commencement of study drug treatment. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration of chemotherapy. 9. Patients must have adequate organ and marrow function within 7 days of first dosing. Hematology re-test results must keep meeting eligibility criteria on Day 1 of treatment prior to dosing. 10. All prior anti-cancer treatment-related toxicities (except alopecia and certain laboratory values) must be = Grade 1 according to the Common Terminology Criteria for Adverse Events at the time of start of treatment. Stable grade 2 peripheral neuropathy secondary to neurotoxicity and/or chronic stable grade 2 radiotherapy related toxicity from prior therapies may be considered on a case by case basis. 11. No extensive radiotherapy (e.g., whole-pelvis, greater than 50% of neuroaxis, whole abdomen, whole body) within 12 months prior to start of study treatment. 12. No bone marrow transplantation within 3 years prior to start of study treatment. 13. Women and man of child bearing potential practicing an acceptable method of birth control during the study and at least 3 months after completion. 14. Female patient of childbearing potential has a negative serum pregnancy test within 7 days of first dose. 15. Understanding study procedures and willingness to comply for the entire length of the study and to provide written informed consent. 16. Patient has previously received maximum 3 regimens of systemic antineoplastic therapies. Exclusion Criteria: 1. Current evidence of active and uncontrolled infection. 2. Known Cirrhosis. 3. Treatment refractory hypertension (blood pressure of systolic> 150 mmHg and/or diastolic > 95 mm Hg) which cannot be controlled by anti-hypertensive therapy; 4. A history or evidence of current Class IV congestive heart failure. 5. Current left ventricular ejection fraction < 50% 6. A history of acute coronary syndromes, coronary angioplasty. 7. Use of nonsteroidal anti-inflammatory drugs - including Aspirin - and/or any steroids within 7 days prior to start of study treatment (excluding eye drops and ointments). Those medications must be stopped or replaced by another equivalent permitted medication at least 7 days prior to Day 1. Those medications will be allowed within 7 days prior to start of treatment only if required as premedication prior to CT scan for patients who are allergic to the contrast media. 8. Patient has a known hypersensitivity to the components of study drug, its analogs, or drugs of similar chemical or biologic composition. 9. Patients with known brain metastases. 10. Patient has known psychiatric or substance abuse disorders that is uncontrolled and would interfere with cooperation with the requirements of the trial. 11. Patient is Human Immunodeficiency virus (HIV)-positive. 12. Evidence of active bleeding or bleeding diathesis, including blood or platelet transfusion within 14 days of the commencement of study treatment. 13. Patients with known chronic active hepatitis, hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. 14. Any known autoimmune disorders other than hypothyroidism or B12 deficiency. 15. Female subjects who are pregnant or nursing. 16. Use of alternative medicine (products only) and Herbal drugs with cancer treatment intent is not allowed within 7 days prior to start of study treatment and during the study. |
Country | Name | City | State |
---|---|---|---|
Israel | Rambam MC | Haifa | |
Israel | Sheba Medical Center | Ramat-Gan |
Lead Sponsor | Collaborator |
---|---|
Efranat Ltd. |
Israel,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Adverse Events that meets the DLT definition | During first course of treatment (up to 4 weeks) | ||
Primary | Percentage of participants with Adverse Events grade 3-4 | During two courses of treatment (up to 8 weeks) |
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