- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02270372
Study of ONT-10 and Varlilumab to Treat Advanced Ovarian or Breast Cancer
A Phase 1b Study of ONT 10 and Varlilumab in Patients With Advanced Ovarian Cancer or Breast Cancer
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a two-part Phase 1b, open-label study of ONT 10 administered in combination with varlilumab. Two different doses of varlilumab will be studied in combination with the single agent recommended dose of ONT 10. Intermediate and/or lower doses of varlilumab or ONT-10 may also be studied at the recommendation of the safety monitoring committee (SMC). Treatment will be administered in cycles of 12 weeks each. All patients will receive a single dose of cyclophosphamide on Day -3. During Cycle 1, patients will receive ONT-10 administered SC once per week for 8 weeks followed by ONT-10 once every 6 weeks starting with Cycle 2, in combination with varlilumab administered IV once every 3 weeks x 3 doses, and then once every 6 weeks for cycles 2 through 5.
Each cohort will enroll an initial group of 6 evaluable patients with either breast or ovarian carcinoma. Initial enrollment into a cohort will be staggered, with the first patient treated in any new cohort to be followed for a minimum of two weeks for the occurrence of Unacceptable Toxicity prior to enrollment of the remaining 5 patients. Subsequent enrollment into a cohort may then continue without a staggered schedule until 6 patients treated are considered evaluable. Up to 24 additional evaluable patients may be enrolled and treated in Part 2 at the RD of varlilumab and ONT-10 identified in Part 1, including approximately equal numbers of patients with breast carcinoma (n~12) and ovarian carcinoma (n~12). Treatment in Part 2 will follow the same schedule as in Part 1.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Alabama
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Birmingham, Alabama, United States, 35294
- Uab Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado
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New York
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New York, New York, United States, 10016
- NYU Perlmutter Cancer Center
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Be at least 18 years of age at the time of consent
- Life expectancy of at least 6 months, in the opinion of the investigator
- Have histologically confirmed breast or ovarian carcinoma
- Have evidence of persistent, recurrent, or progressive disease for which there is no known or established treatment available with curative intent, after at least one course of systemic therapy for locally advanced or metastatic disease , including chemotherapy, targeted therapy (small molecule or antibody based), or hormonal therapy
- Measurable or evaluable disease by RECIST 1.1
- ECOG performed status of 0 or 1
- Adequate hematologic function defined by:
- WBC count ≥ 3.0 x 103 cells/µL
- Lymphocyte count ≥ 0.8 x 103 cells/µL
- Platelet count ≥ 75 x 103 /µL, and
- Hemoglobin ≥ 9 g/dL
- Have renal and hepatic function as defined by:
- AST and ALT ≤ 2.5 X ULN
- Total bilirubin ≤ 1.5 X ULN. Patients with elevated bilirubin known to be due to Gilbert's disease may be enrolled after approval from the medical monitor, and
- Creatinine clearance ≥ 50 mL/min
- If female of child bearing potential, have a negative pregnancy test at screening
- If fertile male or female of child-bearing potential, agree to consistently use a highly effective method of birth control (including birth control pills, barrier device, or intrauterine device, abstinence or other methods prescribed by a licensed healthcare provider) from the time of consent through 70 days following the last dose of study drug
- Patient or a legally authorized representative of a patient must be able and willing to sign informed consent document that has been approved by an IRB
Exclusion Criteria:
- Has medical, social, or psychological factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures
- Is pregnant, breastfeeding, or planning a pregnancy
- Has received treatment with any systemic anticancer therapy, wide-field radiation, or experimental agent within 4 weeks of receiving cyclophosphamide on Day -3, with the exception of anticancer hormonal therapy, which may not be given within 2 weeks of receiving cyclophosphamide on Day -3. All residual toxicity related to prior anticancer therapies (excluding vitiligo, endocrinopathies on stable replacement therapy, alopecia and Grade 2 fatigue) must resolve to Grade 1 severity or less or return to baseline prior to receipt of study treatment.
- Has received treatment with focal radiotherapy within 2 weeks, or radiopharmaceuticals (e.g., strontium, samarium) within 8 weeks of receiving cyclophosphamide on Day -3
- Has untreated or uncontrolled CNS metastases, including patients who require glucocorticoid therapy for CNS metastases
- Has received prior treatment with ONT-10 or varlilumab, or prior treatment with other MUC1 vaccines or CD27-targeted agents
- Has active autoimmune disease or a documented history of autoimmune disease, or history of potential autoimmune syndrome that required systemic steroids or immunosuppressive medications, except for patients with vitiligo, endocrinopathies, type 1 diabetes, or patients with resolved childhood asthma/atopy or other syndromes which would not be expected to recur in the absence of an external trigger (e.g., drug-related serum sickness or post-streptococcal glomerulonephritis). Patients with mild asthma who require intermittent use of bronchodilators (such as albuterol) who have not been hospitalized for asthma in the preceding 3 years will not be excluded from this study.
- Has recognized immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia, and/or other hereditary congenital immunodeficiencies
Has any pre-existing medical condition requiring systemic chronic steroid or immunosuppressive therapy
a) Inhaled corticosteroids for COPD or topical steroids are allowed
- Known to be positive for HIV, or to have active hepatitis B, or hepatitis C, or have active infection of any kind requiring systemic therapy
- Administration of any other vaccine ≤ 4 weeks of receiving cyclophosphamide on Day -3
- Underlying medical condition that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination of adverse events. This includes other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancer; or any other cancer from which the patient has been disease-free for at least 3 years.
- Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension (persistent systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) or arrhythmia, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or myocardial infarction within 6 months prior to the first dose of study treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Drug Combination
The drug combination of ONT-10 and varilumab
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ONT-10 a liposomal synthetic glycopolypeptide MUC1 targeted antigen formulated with PET Lipid A adjuvant. Varlilumab is a recombinant, fully human mAb of the IgG1κ isotype that specifically binds human CD27. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events as a measure of safety and tolerability
Time Frame: Cycles of 12 weeks
|
Assessment of the adverse event profile as an indication of overall safety and tolerability of the combination treatment with ONT-10 and varlilumab
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Cycles of 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immune Response to MUC1
Time Frame: 8 weeks on a weekly basis, followed by every 6 weeks
|
Determine the immune response of the drug combination of varlilumab and ONT-10 to MUC1 specific humoral and cellular responses.
|
8 weeks on a weekly basis, followed by every 6 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Breast Diseases
- Breast Neoplasms
- Carcinoma
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
Other Study ID Numbers
- ONT-10-104
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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