A Two-arm, Single Center Phase 1b Trial of Bavituximab Plus Ipilimumab in Advanced Melanoma Patients

NCT01984255 | Terminated Phase 1 DMC

• 2 other identifiers: STU 102013-007SCCC-05613
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Open label, two-arm, randomized, two agent, single center trial.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Toxicities

  Toxicities will be assessed via NCI's CTCAE v4.1 toxicity criteria. Dose limiting toxicities (DLTs) will be defined as drug-related grade 3-5 adverse events experienced within the first 12 weeks of study treatment. The maximal tolerated dose (MTD) will be exceeded if more than 30% of patients on the study experience DLTs.

  12 weeks

Secondary Outcomes (1)

• Disease control rate (DCR)

  Months of Survival (measured at weeks 15, 21, and 27)

Study Arms (2)

A- Bavituximab plus Ipilimumab

ACTIVE COMPARATOR

Arm A-Interventions Drug: Bavituximab Dose:3mg/kg IV over 90 minutes weekly x 2 followed by Bavituximab 3mg/kg IV over 90 minutes weekly Duration-x 12 weeks plus Drug :Ipilimumab 3mg/kg IV over 90 minutes every 3 weeks Duration-x 4.weeks

Drug: Arm A-Bavituximab 3mg/kg IV over 90 minutes weekly x 3 followed by Bavituximab 3mg/kg IV over 90 minutes weekly x 12 plus ipilimumab 3mg/kg IV

Arm B Ipilimumab

EXPERIMENTAL

Arm B-Interventions Drug- I3mg/kg IV over 90 minutes day 1 followed three weeks later by Drug: Ipilimumab every 3 weeks x 3weeks. Total number of treated patients will be 8.

Drug: Arm B-Ipilimumab 3mg/kg IV over 90 minutes day 1 followed three weeks later by ipilimumab every 3 weeks x 3.

Interventions

Arm A-Bavituximab 3mg/kg IV over 90 minutes weekly x 3 followed by Bavituximab 3mg/kg IV over 90 minutes weekly x 12 plus ipilimumab 3mg/kg IV DRUG

Bavituximab 3mg/kg IV over 90 minutes weekly x 3 followed by Bavituximab 3mg/kg IV over 90 minutes weekly x 12 plus ipilimumab 3mg/kg IV over 90 minutes every 3 weeks x 4. Total number of treated patients will be 16.

A- Bavituximab plus Ipilimumab

Arm B-Ipilimumab 3mg/kg IV over 90 minutes day 1 followed three weeks later by ipilimumab every 3 weeks x 3. DRUG

Ipilimumab 3mg/kg IV over 90 minutes day 1 followed three weeks later by ipilimumab every 3 weeks x 3. Total number of treated patients will be 8.

Arm B Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic diagnosis of unresectable or metastatic melanoma. For unknown primary disease, diagnosis of metastatic disease by cytology FNA (Fine Needle Aspiration) is not acceptable.
• Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab or bavituximab.
• Subjects must have measurable disease as defined by irRC. All sites must be evaluated within 4 weeks prior to beginning therapy.
• Age ≥ 18 years.
• Performance status ECOG (Eastern Cooperative Oncology Group) 0-2.
• Adequate organ and marrow function as defined below:
• leukocytes ≥ 2,000/mcL (Microliter)
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcl
• total bilirubin \< 3X (times) institutional upper limit of normal
• AST (Aspartate Aminotransferase) (SGOT)/ALT (Alanine Aminotransferase)(SPGT) ≤ 2.5 X institutional upper limit of normal
• creatinine \< 3X institutional upper limit of normal
• hemoglobin \>8g/dL
• Ability to understand and the willingness to sign a written informed consent.
• Subjects must be willing to undergo tumor biopsy pretreatment and at weeks 3 and 15.

You may not qualify if:

• No concomitant therapy with any of the following: IL2 (Interleukin 2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids; all such therapies must have been discontinued \>4weeks.
• No infection with HIV and no active infection with hepatitis B and no active or chronic infection with hepatitis C. Due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown.
• Subjects with active CNS (Central nervous system) disease are excluded. Patient with brain metastases previously treated with surgery or stereotactic radiosurgery and with confirmed SD for \>8 weeks are allowed.
• Subjects are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing.
• Any concurrent medical condition requiring the use of systemic steroids is not permitted (the use of inhaled or topic steroids is permitted).
• Subjects are excluded for receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks (28 days) prior to or after any dose of ipilimumab.
• Subjects are excluded if they have a history of prior treatment with ipilimumab, CD137 agonist , CTLA-4 inhibitor (Cytotoxic T-Lymphocyte Antigen 4) or agonist or bavituximab.
• Patients are excluded if they have a history of autoimmune disease except controlled and stable autoimmune thyroiditis. The excluded autoimmune diseases include acute disseminated encephalomyelitis, Addison's disease, alopecia universalis, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, asthma, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune hypoparathyroidism, autoimmune hypophysitis, autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune thrombocytopenic purpura, Behcet's disease, bullous pemphigoid, celiac disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, Crohn's disease, dermatomyositis, dysautonomia, eczema, epidermolysis bullossa acquisita, gestational pemphigoid, giant cell arteritis, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease-except as noted above, IgA nephropathy (Berger's disease), inflammatory bowel disease, interstitial cystitis, Kawasaki's disease, Lambert-Eaton myasthenia syndrome, lupus erythematosis, chronic Lyme disease, Meniere's syndrome, Mooren's ulcer, Morphea, multiple sclerosis, myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome, optic neuritis, Ord's thyroiditis, pemphigus, pernicious anemia, polyarteritis nodosa, polyarthritis, polyglandular autoimmune syndrome, primary biliary cirrhosis, psoriasis, Reiter's syndrome, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, Stiff-Person syndrome, Takayasu's arteritis, ulcerative colitis, Vogt- Kovanagi-Harada disease, vulvodynia, and Wegener's granulomatosis.
• Subjects are excluded with history of thromboembolic events, clinically significant bleeding-gross hematuria, hemoptysis, or gastrointestinal bleeding, history of bleeding diathesis or hypercoagulable state, ongoing therapy with anticoagulants or non-steroidal anti-inflammatory drugs, or prior exposure to chimeric antibodies.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9179, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Arthur Frankel, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2013
• First Posted: November 14, 2013
• Study Start: April 1, 2014
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 29, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)