A Study of Intravenous XMT-1001 in Patients With Advanced Solid Tumors

Sponsor

Mersana Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00455052

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

2.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer Non-small Cell Lung Cancer	Drug: XMT-1001	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous XMT-1001 in Patients With Advanced Solid Tumors

Actual Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XMT-1001 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.	Drug: XMT-1001 XMT-1001 is administered as an IV infusion once every 21 days. This expansion of the Phase 1 study is to confirm the MTD. Other Names: MER-1001

Arm

Intervention/Treatment

Experimental: XMT-1001

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.

Drug: XMT-1001

XMT-1001 is administered as an IV infusion once every 21 days. This expansion of the Phase 1 study is to confirm the MTD.

Other Names:

MER-1001

Outcome Measures

Primary Outcome Measures

Adverse Events [Every 7 days in each 21 day cycle]

Secondary Outcome Measures

Tumor response [Every 2 cycles]
Time to tumor progression [Every 2 cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TGen Clinical Research Services at Scottsdale Healthcare	Scottsdale	Arizona	United States	85258
2	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
3	Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46219
4	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
5	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
6	New York Oncology Hematology	New York	New York	United States	12208
7	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon	United States	97477
8	Institute of Translational Oncology Research	Greenville	South Carolina	United States	29605
9	Texas Oncology - Tyler	Tyler	Texas	United States	75702
10	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
11	Evergreen Hematology & Oncology	Spokane	Washington	United States	99218
12	Vancouver Cancer Center	Vancouver	Washington	United States	98684

Sponsors and Collaborators

Mersana Therapeutics

Investigators

Principal Investigator: Edward Sausville, MD, University of Maryland Greenebaum Cancer Center
Principal Investigator: Glen J Weiss, MD, TGen Clinical Research Services at Scottsdale Healthcare
Principal Investigator: Lawrence Garbo, MD, New York Oncology Hematology
Principal Investigator: Allen Lee Cohn, MD, Rocky Mountain Cancer Centers
Principal Investigator: Paul R. Conkling, MD, Virginia Oncology Associates
Principal Investigator: William J Edenfield, MD, Institute for Translational Oncology Research
Principal Investigator: Donald A. Richards, MD, Texas Oncology - Tyler
Principal Investigator: John R. Caton, MD, Willamette Valley Cancer Institute and Research Center
Principal Investigator: David A. Smith, MD, Northwest Cancer Specialists - Vancouver Cancer Center
Principal Investigator: Hillary H. Wu, MD, Central Indiana Cancer Centers
Principal Investigator: Fadi Braiteh, MD, Comprehensive Cancer Centers of Nevada
Principal Investigator: Stephen Anthony, MD, Evergreen Hematology & Oncology