Recruitment

Recruitment Status
Completed
Estimated Enrollment
46

Inclusion Criterias

Female patient of childbearing potential has a negative serum pregnancy test within 7 days of first dose.
ECOG Performance Status 0 or 1.
Women and man of child bearing potential practicing an acceptable method of birth control during the study and at least 3 months after completion.
...
Female patient of childbearing potential has a negative serum pregnancy test within 7 days of first dose.
ECOG Performance Status 0 or 1.
Women and man of child bearing potential practicing an acceptable method of birth control during the study and at least 3 months after completion.
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.
Estimated life expectancy of at least 4 months.
Measurable disease (i.e., present with at least one measurable lesion per modified RECIST, version 1.1).
Understanding study procedures and willingness to comply for the entire length of the study and to provide written informed consent.
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.
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.
BMI: 18-36.
Age: 18-80 years.
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.
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.
Patient has previously received maximum 3 regimens of systemic antineoplastic therapies.
No bone marrow transplantation within 3 years prior to start of study treatment.

Exclusion Criterias

Treatment refractory hypertension (blood pressure of systolic> 150 mmHg and/or diastolic > 95 mm Hg) which cannot be controlled by anti-hypertensive therapy;
Patients with known chronic active hepatitis, hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers.
Patient is Human Immunodeficiency virus (HIV)-positive.
...
Treatment refractory hypertension (blood pressure of systolic> 150 mmHg and/or diastolic > 95 mm Hg) which cannot be controlled by anti-hypertensive therapy;
Patients with known chronic active hepatitis, hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers.
Patient is Human Immunodeficiency virus (HIV)-positive.
Patient has a known hypersensitivity to the components of study drug, its analogs, or drugs of similar chemical or biologic composition.
Evidence of active bleeding or bleeding diathesis, including blood or platelet transfusion within 14 days of the commencement of study treatment.
A history of acute coronary syndromes, coronary angioplasty.
Any known autoimmune disorders other than hypothyroidism or B12 deficiency.
Patient has known psychiatric or substance abuse disorders that is uncontrolled and would interfere with cooperation with the requirements of the trial.
A history or evidence of current Class IV congestive heart failure.
Patients with known brain metastases.
Known Cirrhosis.
Female subjects who are pregnant or nursing.
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.
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.
Current evidence of active and uncontrolled infection.
Current left ventricular ejection fraction < 50%

Summary

Conditions
Solid Tumors
Type
Interventional
Phase
Phase 1
Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 80 years
Gender
Both males and females

Description

Part 1: Eligible subjects will be assigned, successively in order of accrual, to one of the three cohorts, to receive intramuscular (IM) injections of EF-022, once weekly for two courses of treatment. Each course will consist of 4 injections with one week intervals (total: 8 weeks of treatment). Dos...

Part 1: Eligible subjects will be assigned, successively in order of accrual, to one of the three cohorts, to receive intramuscular (IM) injections of EF-022, once weekly for two courses of treatment. Each course will consist of 4 injections with one week intervals (total: 8 weeks of treatment). Dose escalation will only proceed in the absence of dose-limiting toxicity (DLT) during course 1. For this purpose, each cohort will only begin its first course of EF-022 when the cohort preceding it has successfully completed its first 4-week treatment course without any signs of DLT. During this first course, should 1/3 patients experience DLT, dose escalation for the next cohort will not be authorized; the next cohort will receive the same dose as the one preceding it. If 2 patients or more of all patients treated with a given dose develop DLT, dose escalation will be halted and no more patients will be treated at the DLT dose. The value of MTD will be defined as the EF-022 dose below the dose at which DLT was seen for at least 2 subjects. Upon determination of the MTD, an additional cohort will be opened (confirmatory cohort) and treated with two courses of that dose. Part 2: During the expanded cohort, 24 Patients will be allocated to receive either 100ng, 500ng or 1000ng weekly treatment as detailed below: The first 18 patients will be assigned to alternating doses of either 100ng or 500ng in a sequential manner (each patient will be assigned to a single dose), with the caveat that given indications should be assigned equally, as much as possible, between these two doses. Interim analysis will be performed once the 12th patient reaches Day 57 and the CT results as well as PD analysis are available for at least 12 patients, while at least 18 patients have begun study treatment. A decision regarding adding a 1000ng dose cohort vs. continuing with the 100ng and 500ng doses will be based on a discussion of the interim analysis results. Each patient will receive 2 courses of treatment, i.e. weekly injections for a total period of 8 weeks, followed by a follow-up period of up to 12 months from the start of treatment (Day 1). Continuation of treatment after the second course will be at the discretion of the investigator. Patients who will continue extended treatment post course 2 will keep the weekly injection dosage mode and continue therapy until disease progression, development of unacceptable toxicities, non-compliance, inter-current illness that prevents treatment continuation, withdrawal of consent, or change in subject condition that renders the subject unacceptable for further treatment. All study patients who completed at least two courses of treatment will be followed up until 12 months from day 1 of treatment.

Inclusion Criterias

Female patient of childbearing potential has a negative serum pregnancy test within 7 days of first dose.
ECOG Performance Status 0 or 1.
Women and man of child bearing potential practicing an acceptable method of birth control during the study and at least 3 months after completion.
...
Female patient of childbearing potential has a negative serum pregnancy test within 7 days of first dose.
ECOG Performance Status 0 or 1.
Women and man of child bearing potential practicing an acceptable method of birth control during the study and at least 3 months after completion.
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.
Estimated life expectancy of at least 4 months.
Measurable disease (i.e., present with at least one measurable lesion per modified RECIST, version 1.1).
Understanding study procedures and willingness to comply for the entire length of the study and to provide written informed consent.
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.
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.
BMI: 18-36.
Age: 18-80 years.
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.
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.
Patient has previously received maximum 3 regimens of systemic antineoplastic therapies.
No bone marrow transplantation within 3 years prior to start of study treatment.

Exclusion Criterias

Treatment refractory hypertension (blood pressure of systolic> 150 mmHg and/or diastolic > 95 mm Hg) which cannot be controlled by anti-hypertensive therapy;
Patients with known chronic active hepatitis, hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers.
Patient is Human Immunodeficiency virus (HIV)-positive.
...
Treatment refractory hypertension (blood pressure of systolic> 150 mmHg and/or diastolic > 95 mm Hg) which cannot be controlled by anti-hypertensive therapy;
Patients with known chronic active hepatitis, hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers.
Patient is Human Immunodeficiency virus (HIV)-positive.
Patient has a known hypersensitivity to the components of study drug, its analogs, or drugs of similar chemical or biologic composition.
Evidence of active bleeding or bleeding diathesis, including blood or platelet transfusion within 14 days of the commencement of study treatment.
A history of acute coronary syndromes, coronary angioplasty.
Any known autoimmune disorders other than hypothyroidism or B12 deficiency.
Patient has known psychiatric or substance abuse disorders that is uncontrolled and would interfere with cooperation with the requirements of the trial.
A history or evidence of current Class IV congestive heart failure.
Patients with known brain metastases.
Known Cirrhosis.
Female subjects who are pregnant or nursing.
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.
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.
Current evidence of active and uncontrolled infection.
Current left ventricular ejection fraction < 50%

Locations

Haifa, 31096
Ramat-Gan, 52621
Haifa, 31096
Ramat-Gan, 52621

Tracking Information

NCT #
NCT02052492
Collaborators
Not Provided
Investigators
Not Provided