A First in Man Study of MABp1 in Patients With Advanced Cancers

Study Overview
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Brief Summary
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The purpose of this study is to block interleukin-1 alpha activity with a True Human monoclonal antibody, thus interrupting the inflammatory response that supports tumor growth/metastasis and which drives the cachexic process. An adaptive design will be employed which will allow for the exploration of different dosing regimens, as well as tumor types that show preliminary evidence of efficacy.

Official Title
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A Phase 1 Study of MABp1 in Patients With Advanced Cancers

Conditions
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Advanced Cancers

Intervention / Treatment
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* Drug: MABp1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pathologically confirmed advanced malignancy that is metastatic or unresectable and which is refractory to standard therapy or for which thee is no standard therapy that provides benefits for >/= 3 months measurable or non-measurable disease at baseline at least 4 weeks since the last dose of chemotherapy, radiation therapy, immunotherapy, or surgery; at least 6 weeks for therapy which is known to have delayed toxicity; at least 4 weeks since treatment with biologic/targeted therapies; at least 2 weeks since last hormonal therapy will not be treated with any other chemotherapy, immunotherapy, radiotherapy or investigational drug while enrolled on this protocol age >/= 18 year, male or female Eastern Cooperative Oncology Group performance status 0,1,or 2 Serum potassium and magnesium levels within institutional normal limits. Total serum calcium or ionized calcium level must be greater than or equal to the low limit of normal. Adequate renal function, defined by serum creating </= 1.5 x ULN Adequate hepatic function Adequate bone marrow function WOCBP, a negative serum pregnancy test result at screening. WOCBP or men whose sexual partners are WOCBP who are willing to use an acceptable method of contraception for at least 1 month prior to study entry, for the duration of the study, and for at least 3 months after the last dose of study medication Signed and dated IRB approved ICF before any protocol specific screening procedures are performed Exclusion Criteria: serious uncontrolled medical disorder or active infection which would impair the patient to receive protocol therapy. Uncontrolled or significant cardiovascular diseae dementia or altered mental status that would prohibit the understanding or rendering of informed consent not recovered from the adverse effects of prior therapy at the time of enrollment </= grade 1 symptomatic brain metastases which are either untreated or uncontrolled by surgery and or radiotherapy received extensive prior radiation therapy to the bone marrow immunocompromised, including subjects know to be infected with HIV history of hypersensitivity to compounds of similar chemical or biologic composition to the antibody women how are pregnant or breastfeeding WOCBP or men whose sexual partners are WOCBP who are unwilling or unable to use an acceptable method of contraception for at least 1 month prior to study entry, for the duration of the study, and for at least 3 months after the last dose of study medication

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MTD<br>The study will utilize a standard 3+3 design for dose escalation. Once the maximum tolerated dose has been reached, an expansion cohort, as well as tumor specific expansion cohorts will be explored. | Drug: MABp1<br>* 0.25 mg/kg,0.75 mg/kg,1.25 mg/kg, 3.75 mg/kg IV (in the vein) on day 1 of each 21 day cycle until progression or unacceptable toxicity develops.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  | one year | 
| Cachexia Response | Change in LBT as measured by DEXA | 8 weeks |