Back to resultsA Study of Intravenous XMT-1001 in Patients With Advanced Solid Tumors
Primary Purpose
Small Cell Lung Cancer, Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
XMT-1001
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Cancer focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- At least 18 years old
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.
- 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.
- 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.
- 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.
- At least 42 days since administration of mitomycin or nitrosoureas, and 28 days since any other chemotherapy, investigational agent, and/or radiation therapy.
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
- Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
- Have a life expectancy of at least 3 months.
- Have signed an informed consent form.
Sites / Locations
- TGen Clinical Research Services at Scottsdale Healthcare
- Rocky Mountain Cancer Centers
- Central Indiana Cancer Centers
- University of Maryland, Greenebaum Cancer Center
- Comprehensive Cancer Centers of Nevada
- New York Oncology Hematology
- Willamette Valley Cancer Institute and Research Center
- Institute of Translational Oncology Research
- Texas Oncology - Tyler
- Virginia Oncology Associates
- Evergreen Hematology & Oncology
- Vancouver Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
XMT-1001
Arm Description
XMT-1001 is administered I.V. every 21 days. Groups of 3 patients are given one dose and the dose increases for each group. The first dose level is 17 mg/m^2, the next dose level is 30 mg/m^2, followed by dose levels: 50 mg/m^2, 80 mg/m^2, 120 mg/m^2, 150 mg/m^2, and 190 mg/m^2 until disease progressions or unacceptable side effects are experienced.
Outcomes
Primary Outcome Measures
Adverse Events
Secondary Outcome Measures
Tumor response
Time to tumor progression
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00455052
Brief Title
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
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
March 2011 (Actual)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mersana Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
XMT-1001
Arm Type
Experimental
Arm Description
XMT-1001 is administered I.V. every 21 days. Groups of 3 patients are given one dose and the dose increases for each group. The first dose level is 17 mg/m^2, the next dose level is 30 mg/m^2, followed by dose levels: 50 mg/m^2, 80 mg/m^2, 120 mg/m^2, 150 mg/m^2, and 190 mg/m^2 until disease progressions or unacceptable side effects are experienced.
Intervention Type
Drug
Intervention Name(s)
XMT-1001
Other Intervention Name(s)
MER-1001
Intervention Description
XMT-1001 is administered as an IV infusion once every 21 days. This expansion of the Phase 1 study is to confirm the MTD.
Primary Outcome Measure Information:
Title
Adverse Events
Time Frame
Every 7 days in each 21 day cycle
Secondary Outcome Measure Information:
Title
Tumor response
Time Frame
Every 2 cycles
Title
Time to tumor progression
Time Frame
Every 2 cycles
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At least 18 years old
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.
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.
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.
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.
At least 42 days since administration of mitomycin or nitrosoureas, and 28 days since any other chemotherapy, investigational agent, and/or radiation therapy.
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
Have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.
Have a life expectancy of at least 3 months.
Have signed an informed consent form.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Sausville, MD
Organizational Affiliation
University of Maryland Greenebaum Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Glen J Weiss, MD
Organizational Affiliation
TGen Clinical Research Services at Scottsdale Healthcare
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lawrence Garbo, MD
Organizational Affiliation
New York Oncology Hematology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Allen Lee Cohn, MD
Organizational Affiliation
Rocky Mountain Cancer Centers
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul R. Conkling, MD
Organizational Affiliation
Virginia Oncology Associates
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William J Edenfield, MD
Organizational Affiliation
Institute for Translational Oncology Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Donald A. Richards, MD
Organizational Affiliation
Texas Oncology - Tyler
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John R. Caton, MD
Organizational Affiliation
Willamette Valley Cancer Institute and Research Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David A. Smith, MD
Organizational Affiliation
Northwest Cancer Specialists - Vancouver Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hillary H. Wu, MD
Organizational Affiliation
Central Indiana Cancer Centers
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fadi Braiteh, MD
Organizational Affiliation
Comprehensive Cancer Centers of Nevada
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen Anthony, MD
Organizational Affiliation
Evergreen Hematology & Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
TGen Clinical Research Services at Scottsdale Healthcare
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Central Indiana Cancer Centers
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46219
Country
United States
Facility Name
University of Maryland, Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
New York Oncology Hematology
City
New York
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
Institute of Translational Oncology Research
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Evergreen Hematology & Oncology
City
Spokane
State/Province
Washington
ZIP/Postal Code
99218
Country
United States
Facility Name
Vancouver Cancer Center
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16026008
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.
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A Study of Intravenous XMT-1001 in Patients With Advanced Solid Tumors
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