A Two-Arm, Single Center Phase IB Trial of Bavituximab plus Ipilimumab in Advanced Melanoma Patients

Summary

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

Study Product(s), Dose, Route, Regimen:
Bavituximab 3mg/kg iVqwk x 14 plus ipilimumab 3mg/kg iVq3wk x 4 or ipilimumab 3mg/kg iVq3wk x 4

administration Schedule:
Patients will be randomized to one of the following arms:

arm a-Bavituximab 3mg/kg iV over 90 minutes weekly x 2 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.

arm B-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.

Randomization:
There will be a 2:1 randomization of patients to have a 3 week lead-in treatment with bavituximab followed by combination therapy of ipilimumab + bavituximab versus ipilimumab alone. The assigned treatment will be given once subject is registered successfully.


endpoints:
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.

DCR will be measured by irRC at weeks 15, 21, 27 using the published algorithm. Disease control rate (DCR) includes complete response (CR), Partial response (PR) and stable disease (SD). Months of suvival (MoS) is measured from date of entry into protocol.

Tumor MDSC, TaM and Treg content will be measured by iHC. Circulating MDSC, TaM and Treg content will be measured by flow cytometry.

Peripheral blood cytokines will be measured by eia.

Participant Eligibility

1. Histologic diagnosis of unresectable or metastatic melanoma. For unknown primary disease, diagnosis of metastatic disease by cytology FNA is not acceptable.

2.Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab or bavituximab.

3. Subjects must have measurable disease as defined by irRC. All sites must be evaluated within 4 weeks prior to beginning therapy.

4. Age >= 18 years.

5. Performance status ECOG 0-2.

6. Adequate organ and marrow function as defined below:
- leukocytes >= 2,000/mcL
- absolute neutrophil count >= 1,500/mcL
- platelets >= 100,000/mcl
- total bilirubin < 3X institutional upper limit of normal
- AST(SGOT)/ALT(SPGT) <= 2.5 X institutional upper limit of normal
- creatinine < 3X institutional upper limit of normal
-hemoglobin >8g/dL

7. Ability to understand and the willingness to sign a written informed consent.

8. Subjects must be willing to undergo tumor biopsy pretreatment and at weeks 3 and 15.

9. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).