Clinical trial NCT01011972: A Study of Intravenous XMT-1107 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of the Safety and Pharmacokinetics of XMT-1107 Administered as an Intravenous Infusion Once Every Three Weeks to Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Metastasis
Keywords: Dose escalation
XMT-1107
1107
Tumor
Phase 1
Fumagillol
PHF
Fleximer
cancer
maximum tolerated dose
MTD
Lead sponsor: Mersana Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-11-11
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is an open-label, ascending-dose study of XMT-1107 administered intravenously over 90 minutes every 21 days (1 cycle). Blood sampling for PK analyses will be performed immediately prior to dosing and after dosing. Adverse events will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria (CTC) version 4.0 (CTCAE v4.0)

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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:

  1. urine protein creatinine (UPC) ratio ≥ 1.0 at screening OR
  2. 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.
* Patients with history of hematemesis or hemoptysis (defined as having bright red blood of ½ teaspoon or more per episode) ≤ 1 month prior to study enrollment.
* Inadequately controlled hypertension (defined as systolic blood pressure \>140 mm Hg and/or diastolic blood pressure \> 90 mm Hg while on antihypertensive medications). Initiation of antihypertensive agents is permitted provided adequate control is documented at least 1 week prior to beginning study treatment.
* Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) ≤ 6 months prior to Day 1 of treatment.
* History of stroke or transient ischemic attack ≤ 6 months prior to beginning treatment.
* Any prior history of hypertensive crisis or hypertensive encephalopathy.
* History of abdominal fistula or gastrointestinal perforation ≤ 6 months prior to Day 1 of beginning treatment.
* QTc interval \> 470 milliseconds as calculated by Bazett's formula.
* Any issue that, in the opinion of the Investigator, would render the patient unsuitable for study participation.

Primary outcomes:
measure: The primary objective of this study is to determine the maximum tolerated dose of XMT-1107 when given via IV once every three weeks.
timeFrame: Adverse events are assessed during each treatment cycle.
Secondary outcomes:
measure: Assess the pharmacokinetics (PK) of XMT-1107 and its release product
timeFrame: Samples for PK are collected during Cycle 1 and prior to each subsequent treatment cycle
measure: Determine the recommended Phase 2 dose of XMT-1107
timeFrame: Throughout Cycle 1
measure: Assess the safety of XMT-1107.
timeFrame: Throughout Cycle 1
measure: Observe for evidence of anti-tumor activity by XMT-1107.
timeFrame: Course of study
measure: Monitor the effect of XMT-1107 on MetAP2 inhibition in leukocytes from patients
timeFrame: Cycle 1 and Cycle 2
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of MD Greenbaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI)
state: Tennessee
Study officials:
affiliation: Sara Cannon Research Institute
name: Johana Bendell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Geoffrey Shapiro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, Greenbaum Cancer Center
name: Edward Sausville, MD
role: PRINCIPAL_INVESTIGATOR
References: