A Study Evaluating MM-310 in Patients With Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

A Phase-1 Study Evaluating the Safety, Pharmacology and Preliminary Activity of MM-310 in Patients With Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03076372
• Other study ID #: MM-310-01-01-01
• Status: Recruiting
• Phase: Phase 1
• First received: March 1, 2017
• Last updated: February 26, 2018
• Start date: February 22, 2017
• Est. completion date: December 2018

Study information

• Verified date: February 2018
• Source: Merrimack Pharmaceuticals
• Contact: Vasileios Askoxylakis, MD, PhD
• Phone: 617.441.7492
• Email: VAskoxylakis[@]merrimack.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

MM-310 is a liposomal formulation of a docetaxel prodrug that targets the EphA2 receptor on cancer cells. Docetaxel is an approved chemotherapeutic drug.This study is a Phase 1 open-label study of MM-310 in patients with solid tumors. In the first part of the study, MM-310 will be assessed as a monotherapy until a maximum tolerated dose (MTD) is established. After an MTD of MM-310 as a monotherapy is established, an expansion cohort and MM-310 in combination with other therapies will be assessed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have one of the following cancers, for which the patient has either received or been intolerant to all therapy known to confer clinical benefit

• Urothelial carcinoma

• Gastric/gastroesophageal junction/esophageal carcinoma (G/GEJ/E)

• Squamous Cell Carcinoma of the Head and neck (SCCHN)

• Ovarian cancer

• Pancreatic ductal adenocarcinoma (PDAC)

• Prostate adenocarcinoma (PAC)

• Non-small cell lung cancer (NSCLC)

• Small cell lung cancer (SCLC)

• Triple negative breast cancer (TNBC)

• Endometrial carcinoma

• Soft tissue sarcoma subtypes except GIST, desmoid tumors and pleomorphic rhabdomyosarcoma

• Able to provide informed consent, or have a legal representative able and willing to do so

• = 18 years of age

• Availability of a cancerous lesion amenable to biopsy and willing to undergo a pre-treatment biopsy

• ECOG Performance Status of 0 or 1

• Adequate bone marrow reserve as evidenced by:

• ANC > 1,500/µl (unsupported by growth factors) and

• Platelet count > 100,000/µl

• Hemoglobin > 9 g/dL

• Patients must have adequate coagulation function as evidenced by prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) within normal institutional limits

• Adequate hepatic function as evidenced by:

• Serum total bilirubin = ULN

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN.

• Alkaline phosphatase = 2.5 x ULN, unless the elevated alkaline phosphatase is due to bone metastasis.

• In case alkaline phosphatase is >2.5 x ULN patients are eligible for inclusion if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 1.5 x ULN

• Adequate renal function as evidenced by a serum/plasma creatinine < 1.5 x ULN

• Recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy to CTCAE v4.03 grade 1, baseline or less, except for alopecia

• Women of childbearing potential or fertile men and their partners must be willing to abstain from sexual intercourse or to use an effective form of contraception during the study and for 6 months following the last dose of MM-310.

Exclusion Criteria:

• Prior treatment with docetaxel within 6 months of study enrollment

• Pregnant or lactating

• Treatment with systemic anticoagulation (e.g. warfarin, heparin, low molecular weight heparin, anti-Xa inhibitors, etc.) except aspirin

• Any evidence of hematemesis, melena, hematochezia, = grade 2 hemoptysis, or gross hematuria

• Any history of hereditary bleeding disorders

• Presence of an active infection or with an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing, which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome. At the discretion of the investigator, patients with tumor fever may be enrolled

• Known CNS metastases

• Known hypersensitivity to the components of MM-310, or docetaxel

• Prior treatment with MM-310

• Received treatment, within 28 days or 5 half-lives, whichever is shorter, prior to the first scheduled day of dosing, with any investigational agents that have not received regulatory approval for any indication or disease state and all prior clinically significant treatment related toxicities have resolved to Grade 1 or baseline

• Received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (or have not yet recovered from any actual toxicities of the most recent therapy) prior to the first scheduled dose of MM-310

• Received any anti-cancer drug known to have anti-VEGF/VEGFR activity within a period of 5 half-lives of this drug (e.g. 100 days for bevacizumab, 75 days for ramucirumab) prior to the first scheduled dose of MM-310

• Clinically significant cardiac disease, including: NYHA Class III or IV congestive heart failure, unstable angina, acute myocardial infarction within six months of planned first dose, arrhythmia requiring therapy (including torsades de pointes, with the exception of extrasystoles, minor conduction abnormalities, or controlled and well treated chronic atrial fibrillation)

• Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator

• Patients who received organ or allogeneic bone marrow or peripheral blood stem cell transplants

• Chronic use of corticosteroids more than 10mg daily prednisone equivalent during the past 4 weeks prior to planned start of MM-310

• Concomitant use of strong inhibitors of CYP3A

• Patients with peripheral neuropathy of grade 2 or higher

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Carcinoma, Transitional Cell
• Endometrial Carcinoma
• Endometrial Neoplasms
• Gastric Carcinoma
• Head and Neck Neoplasms
• Lung Neoplasms
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Pancreatic Ductal Adenocarcinoma
• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Sarcoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma
• Soft Tissue Sarcoma
• Solid Tumors
• Squamous Cell Carcinoma of the Head and Neck
• Stomach Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• MM-310
MM-310

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Duke University	Durham	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	University California San Francisco	San Francisco	California
United States	Honor Health	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of MM-310 monotherapy administered once every 3 weeks in patients with metastatic solid tumors.		18 months
Secondary	Serum levels of analytes that comprise MM-310		18 months
Secondary	Adverse event profile using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03		18 months
Secondary	Presence of human anti-human antibodies to MM-310		18 months
Secondary	Objective responses based on RECIST v1.1 or other relevant criteria		18 months
Secondary	Disease Control Rate		18 months
Secondary	Progression Free Survival		18 months