Clinical trial NCT00455052: A Study of Intravenous XMT-1001 in Patients With Advanced Solid Tumors
Official title: A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous XMT-1001 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Non-small Cell Lung Cancer
Keywords: XMT-1001
cancer
tumor
camptothecin
Fleximer
polymer
Phase 1
safety
pharmacokinetics
maximum tolerated dose
NSCLC
non-small cell lung cancer
SCLC
small cell lung cancer
Lead sponsor: Mersana Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-04-03
Enrollment: 30
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: This amended expansion phase of the protocol is to further the experience at a dose level of 150 mg CPT eq/m2 in patients with Stage IV non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) and to test for preliminary anti-tumor activity in these tumor types. The MTD was initially defined as 113 mg CPT equivalents(eq)/m2 in the dose escalation part of the study. However, in the initial expansion phase (Protocol Amendment 11), 11 patients (10 NSCLC patients and 1 gastric cancer patients) were dosed at 113 mg CPT eq/m2 and less bone marrow toxicity was observed as compared to more heavily pre-treated patients in the dose escalation part of the study. Therefore, this amended expansion phase will investigate the safety and anti-tumor effects of a dose of 150 mg CPT eq/m2.

The study will also determine:

* The safety and tolerability of XMT-1001 at 150 mg CPT eq/m2
* The pharmacokinetics (PK) of XMT-1001 (how XMT-1001 behaves in the body) in patients Stage IV non-small cell lung carcinoma (NSCLC) and small cell lung cancer
* Evidence of XMT-1001 anti-tumor activity at 150 mg CPT eq/m2

Detailed description: This is an open-label study of XMT-1001 administered intravenously over 4 hours every 21 days (1 Cycle). Blood sampling for PK analyses will be performed immediately prior to dosing, and 9 times after dosing. Patients will be assessed for toxicities known to occur with other drugs of this class, such as bone marrow suppression, elevated liver function enzymes, hemorrhagic cystitis, and diarrhea. Tumor imaging will be performed every 2 cycles.

Eligibility criteria: Inclusion Criteria:

1. At least 18 years old
2. Have histological or cytological documentation of one of the following:

   A. NSCLC with Stage IV disease according to the American Joint Cancer Commission TNM Staging (7th Edition)
   * Have received at least one prior chemotherapy regimen but no more than two chemotherapy regimens for their advanced disease (not containing irinotecan or topotecan).
   * Adjuvant chemotherapy will be considered as a prior chemotherapy regimen only if it is completed less than 6 months prior to enrollment.
   * Treatment with erlotinib or crizotinib as single agents will not be considered as a chemotherapy regimen for purposes of this trial OR B. SCLC with Stage IV (extensive) or recurrent disease after definitive treatment for limited stage disease according to the American Joint Cancer Commission TNM Staging (7th Edition)1
   * Have received at least one prior chemotherapy regimen but no more than two chemotherapy regimens for their advanced disease (not containing irinotecan or topotecan).
   * Adjuvant chemotherapy will be considered as a prior chemotherapy regimen only if it is completed less than 6 months prior to enrollment.
3. Patients must be refractory or resistant to standard therapy or for whom standard therapy is not anticipated to be curative and who have progressed through prior regimens.
4. Patients must have measurable disease with at least one lesion that can be accurately measured by Response Evaluation Criteria in Solid Tumors (RECIST). The lesion size must be ≥20 mm by conventional radiological techniques or ≥10 mm by spiral CT scan. Disease in an irradiated field as the only site of measurable disease is acceptable if there has been a clear progression of the lesion. PET scans are not suitable for providing these measurements. For patients who are sensitive to contrast, MRI may be used.
5. Patients with CNS metastases are acceptable provided that the disease has been treated (e.g. surgery, whole brain radiotherapy, stereotactic radiotherapy etc.) and the patient is stable for at least two weeks and does not require steroids (at least one week off steroids). Anti-seizure medication is allowed at the discretion of the treating physician.
6. At least 42 days since administration of mitomycin or nitrosoureas, and 28 days since any other chemotherapy, investigational agent, and/or radiation therapy.
7. Have the following laboratory values:

   * Absolute neutrophil count (ANC) ≥1500 cells/mm3
   * Platelet count \>100,000 cells/mm3
   * Hemoglobin ≥9.0 g/dL
   * Adequate renal function (serum creatinine ≤2 mg/dL) and creatinine clearance ≥45 mL/min (Calculated by Cockroft and Gault method)
   * Adequate hepatic function (bilirubin ≤1.5 mg/dL)
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the institutional upper limit of normal (ULN, or

     * 5 times the ULN if liver metastases are present)
   * Albumin of \>3.0 g/dL
   * PT and PTT ≤1.5 times the ULN
8. Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
9. Have a life expectancy of at least 3 months.
10. Have signed an informed consent form.

Primary outcomes:
measure: Adverse Events
timeFrame: Every 7 days in each 21 day cycle
Secondary outcomes:
measure: Tumor response
timeFrame: Every 2 cycles
measure: Time to tumor progression
timeFrame: Every 2 cycles
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TGen Clinical Research Services at Scottsdale Healthcare
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: New York Oncology Hematology
state: New York
city: Springfield
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Greenville
country: United States
facility: Institute of Translational Oncology Research
state: South Carolina
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Spokane
country: United States
facility: Evergreen Hematology & Oncology
state: Washington
city: Vancouver
country: United States
facility: Vancouver Cancer Center
state: Washington
Study officials:
affiliation: University of Maryland Greenebaum Cancer Center
name: Edward Sausville, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: TGen Clinical Research Services at Scottsdale Healthcare
name: Glen J Weiss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Oncology Hematology
name: Lawrence Garbo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rocky Mountain Cancer Centers
name: Allen Lee Cohn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Oncology Associates
name: Paul R. Conkling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute for Translational Oncology Research
name: William J Edenfield, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Oncology - Tyler
name: Donald A. Richards, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Willamette Valley Cancer Institute and Research Center
name: John R. Caton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwest Cancer Specialists - Vancouver Cancer Center
name: David A. Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Central Indiana Cancer Centers
name: Hillary H. Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comprehensive Cancer Centers of Nevada
name: Fadi Braiteh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Evergreen Hematology & Oncology
name: Stephen Anthony, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yurkovetskiy AV, Hiller A, Syed S, Yin M, Lu XM, Fischman AJ, Papisov MI. Synthesis of a macromolecular camptothecin conjugate with dual phase drug release. Mol Pharm. 2004 Sep-Oct;1(5):375-82. doi: 10.1021/mp0499306.