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A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas


OBJECTIVES:

Primary

- Define the maximum tolerated dose (MTD) of topoisomerase I inhibitors LMP400 and LMP776
in patients with relapsed solid tumors or lymphomas.

- Define the dose-limiting toxicities and toxicity profile of topoisomerase I inhibitors
LMP400 and LMP776 in these patients.

- Evaluate the effect of topoisomerase I inhibitors LMP400 and LMP776 on the
pharmacodynamic (PD) endpoint, γ-H2AX, in pre- and post-treatment tumor biopsy and skin
tissue samples.

- Compare topoisomerase I inhibitors LMP400 and LMP776 (when administered at the MTD), in
terms of the PD response, defined as the mean percent nuclear area that is γ-H2AX
positive in tumor biopsies, and the risk-benefit relationship, defined by the toxicity
profile vs PD dose-response relationship.

Secondary

- Obtain preliminary evidence of anti-tumor activity of topoisomerase I inhibitors LMP400
and LMP776.

- Characterize the pharmacokinetic profile of topoisomerase I inhibitors LMP400 and
LMP776.

OUTLINE: Patients are alternately assigned to 1 of 2 treatment groups.

- Group I: Patients receive topoisomerase I inhibitor LMP400 IV over 1 hour on days 1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

- Group II: Patients receive topoisomerase I inhibitor LMP776 IV over 1 hour on days 1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity.

Patients undergo blood, urine, tumor tissue, and skin tissue sample collection periodically
for correlative laboratory studies, including pharmacodynamic and pharmacokinetic studies
and γ-H2AX marker expression. Patients may also undergo hair follicle sample collection for
correlative laboratory studies.

After completion of study therapy, patients are followed for 30 days.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed relapsed solid tumor malignancy or Hodgkin or non-Hodgkin
lymphoma

- Metastatic or unresectable disease for which standard curative measures do not
exist or are associated with minimal patient survival benefit

- Measurable or evaluable disease

- Disease amenable to biopsy

- No known brain metastases

- Patients whose brain metastases have remained stable for ≥ 2 months after
treatment AND do not require steroids or anti-seizure medications may be
eligible at the discretion of the investigator

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

- Life expectancy > 3 months

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ 1.5 mg/dL (≤ 2.5 mg/dL for patients with Gilbert's syndrome)

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to, during, and for ≥ 2
months after completion of study therapy

- Willing to undergo skin biopsies

- No clinically significant illness that could compromise participation in the study,
including, but not limited to any of the following:

- Active or uncontrolled infection

- Immune deficiencies

- Known HIV infection requiring antiretroviral therapy

- Hepatitis B or C

- Uncontrolled diabetes

- Uncontrolled hypertension

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- Uncontrolled cardiac arrhythmia

- Psychiatric illness and/or social situation that would limit compliance with
study requirements

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior chemotherapy or biological therapy (6 weeks for
nitrosoureas or mitomycin C; 2 months for UCN-01) and recovered

- No prior tyrosine kinase inhibitors within 5 times the half-life of the inhibitors

- At least 2 weeks since prior administration of a study drug in an exploratory
IND/phase 0 study

- At least 1 month since prior radiotherapy

- Prior topoisomerase I inhibitors allowed

- Concurrent bisphosphonates for any cancer allowed

- Concurrent androgen deprivation therapy for prostate cancer allowed

- No other concurrent investigational agents

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of topoisomerase I inhibitors LMP400 and LMP776

Safety Issue:

Yes

Principal Investigator

Shivaani Kummar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Medical Oncology Branch

Authority:

Unspecified

Study ID:

CDR0000662682

NCT ID:

NCT01245192

Start Date:

January 2010

Completion Date:

Related Keywords:

  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • recurrent adult Hodgkin lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • stage IV mycosis fungoides/Sezary syndrome
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • Waldenstrom macroglobulinemia
  • cutaneous B-cell non-Hodgkin lymphoma
  • adult nasal type extranodal NK/T-cell lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182