Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

Study Overview
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Brief Summary
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This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a 3+3 design, evaluating MM-151 at varying dose levels and frequencies, and subsequently in combination with irinotecan.

Detailed Description
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This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a 3+3 design exploring weekly, bi-weekly, and tri-weekly dosing schedules. Successive MM-151 monotherapy cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified, and subsequently in combination with irinotecan. The study consists of three parts as follows: MM-151 monotherapy dose escalation (Part 1); MM-151 monotherapy expansion cohort in cetuximab-refractory colorectal cancer (Part 2); MM-151 + irinotecan dose escalation (Part 3). It is expected that approximately 4 study sites will participate.

Official Title
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A Phase 1 and Pharmacologic Study of MM-151 in Patients With Refractory Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, Colorectal Cancer, Squamous Cell Head and Neck Cancer, Non Small Cell Lung Cancer, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: MM-151
* Drug: MM-151 + irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy Patients must be > 18 years of age Patients of their legal representatives must be able to understand and sign an informed consent form Patients must have evaluable or measurable tumor(s) Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy. Up to CTCAE Grade 1 is acceptable for patients with known peripheral neuropathy Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-151 (an effective form of contraception is an oral contraceptive or a double barrier method) Exclusion Criteria: Patients for whom potentially curative antineoplastic therapy is available Patients who are pregnant or lactating Patients with an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing. (At the discretion of the investigator, patients with tumor fever may be enrolled.) Patients with untreated and/or symptomatic CNS malignancies (primary or metastatic); patients with CNS metastases who have undergone surgery or radiotherapy, whose disease is stable, and who have been on a stable dose of corticosteroids for at least 2 weeks prior to the first scheduled day of dosing will be eligible for the trial

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: MM-151 Dose Escalation<br>MM-151 Dose escalation frequency - once weekly, once every two weeks, once every three weeks | Drug: MM-151<br>* MM-151<br>|
| Experimental: MM-151 Expansion in KRAS wild type colorectal cancer<br>MM-151 given weekly | Drug: MM-151<br>* MM-151<br>|
| Experimental: MM-151 + irinotecan<br>MM-151 given weekly, irinotecan 180 mg/m2 given once every two weeks | Drug: MM-151 + irinotecan<br>* MM-151 + irinotecan<br>* Other names: camptosar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II dose of MM-151 alone and in combination with irinotecan based either on the maximum tolerated dose (MTD) or maximum dose of 18 mg/kg in patients with advanced solid malignancies. |  | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dose limiting toxicities (DLTs) within a cohort |  | 2 years | 
| Adverse event profile of MM-151 alone and in combination with irinotecan |  | 2 years | 
| Objective response to MM-151 alone and in combination with irinotecan based on RECIST |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, solid tumors, oncology, Phase I, EGFR, EGF receptor (ErbB1), irinotecan