A Study of Intravenous XMT-1107 in Patients With Advanced Solid Tumors

NCT01011972 | Completed Phase 1

• 1 other identifier: MER-1107-001
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

XMT-1107 has been shown in nonclinical studies to slow the growth of tumors. These effects may result from blocking the growth of new blood vessels that help the tumors survive.

Conditions

Neoplasm Metastasis

Keywords

Dose escalation; XMT-1107; 1107; Tumor; Phase 1; Fumagillol; PHF; Fleximer; cancer; maximum tolerated dose; MTD

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to determine the maximum tolerated dose of XMT-1107 when given via IV once every three weeks.

  Adverse events are assessed during each treatment cycle.

Secondary Outcomes (5)

• Assess the pharmacokinetics (PK) of XMT-1107 and its release product

  Samples for PK are collected during Cycle 1 and prior to each subsequent treatment cycle

• Determine the recommended Phase 2 dose of XMT-1107

  Throughout Cycle 1

• Assess the safety of XMT-1107.

  Throughout Cycle 1

• Observe for evidence of anti-tumor activity by XMT-1107.

  Course of study

• Monitor the effect of XMT-1107 on MetAP2 inhibition in leukocytes from patients

  Cycle 1 and Cycle 2

Study Arms (1)

XMT-1107

EXPERIMENTAL

Dose escalation groups of XMT-1107, I.V. (in the arm) beginning at 6 mg/m\^2, doubling in dose to 24 mg/m\^2, then 40 mg/m\^2, then 60 mg/m\^2, then 80 mg/m\^2 with subsequent doses at 33% of the previous until disease progression or unacceptable side effects are experienced.

Drug: XMT-1107

Interventions

XMT-1107 DRUG

6 mg XMT-1107 administered by I.V. (in the vein) administered over 90 min, once every 21 days : until progression or unacceptable toxicity develops

Also known as: conjugated XMT-1191

XMT-1107

Eligibility Criteria

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

You may qualify if:

• Patient must have a histological diagnosis of advanced solid tumor and must be refractory to standard therapy or have no effective therapy.
• Measurable or evaluable disease.
• At least 42 days since administration of mitomycin or nitrosoureas and 28 days since any other chemotherapy, investigational agent, and/or radiation therapy.
• Age ≥ 18 years old.
• Have the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 60 mL/min (Calculated by Cockroft and Gault method. Creatinine clearance (mL/min) = (140-age) x weight (kg)/72 x (serum creatinine in mg/dL) = ml\*\*/min (\*\*for females, multiply results by 0.85))
• Total bilirubin ≤ 1.5 mg/dL or ≤ upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the institutional upper limit of normal (ULN) or ≤ 5 times ULN of liver metastases are present
• Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 times the ULN
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
• Life expectancy of at least 3 months.
• Signed informed written consent.

You may not qualify if:

• Known brain metastases (either currently or previously).
• Peripheral neuropathy ≥ Grade 2.
• Ataxia ≥ Grade 1.
• Cognitive disturbance ≥ Grade 1.
• History of seizures.
• Patients known to be human immunodeficiency virus (HIV) positive.
• Active infections requiring IV antibiotics or serious intercurrent illness, including hepatitis B or C.
• Unstable angina, recent myocardial infarction (within the previous 6 months), or use of ongoing maintenance therapy for life-threatening arrhythmia.
• Known hypersensitivity to this class of drugs.
• Pregnant or nursing women, women who are of childbearing potential and are not using an effective method of either barrier or hormonal contraceptives. Men who are not using an effective method of barrier contraceptive, or who would not be willing to continue to use these effective methods for the duration of the study.
• Patients who have had a major surgical procedure (not including mediastinoscopy), open biopsy, or significant traumatic injury ≤ 4 weeks prior to beginning treatment.
• Patients with proteinuria at screening as demonstrated by either:
• urine protein creatinine (UPC) ratio ≥ 1.0 at screening OR
• urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection, and must demonstrate ≤ 1 g of protein/24 hours to be eligible)
• Patients with a serious non-healing wound, active ulcer, or untreated bone fracture.

Sponsors & Collaborators

• Mersana Therapeutics: lead

Study Sites (4)

University of MD Greenbaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Sarah Cannon Research Institute (SCRI)

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Johana Bendell, MD

  Sara Cannon Research Institute

  PRINCIPAL INVESTIGATOR

• Geoffrey Shapiro, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

• Edward Sausville, MD

  University of Maryland, Greenbaum Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2009
• First Posted: November 11, 2009
• Study Start: March 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 31, 2018

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)