Study of RH-1 in Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00558727
Recruitment Status : Terminated
First Posted : November 15, 2007
Last Update Posted : May 10, 2013
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Brief Summary:

This is a Phase 1, nonrandomized, open-label, dose-escalation study of 3-hour IV infusions of RH-1 administered to patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL).

Treatment will continue until a patient meets criteria for discontinuation.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Non-Hodgkin's Lymphoma Drug: RH-1 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Protocol RH-1-002: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Dose-escalation Study of RH-1 Administered as a 3-hour Intravenous Infusion in Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
Study Start Date : November 2007
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Intervention Details:
    Drug: RH-1
    1.5 mg/m2 to 12 mg/m2, depending on protocol cohort, administered via intravenous (IV) infusion over 3 hours once every 21 days.
    Other Name: 2,5-diaziridinyl-3-[hydroxymethyl]-6-methyl-1,4-benzoquinone

Primary Outcome Measures :
  1. To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of a 3-hour intravenous (IV) infusion of RH-1 administered once every 21 days. [ Time Frame: Study duration ]

Secondary Outcome Measures :
  1. To evaluate the safety and tolerability of 3-hour IV infusions of RH-1. [ Time Frame: Study duration ]
  2. To determine the pharmacokinetic (PK) profile of 3-hour IV infusions of RH-1 administered at escalating doses. [ Time Frame: Study duration ]
  3. To assess preliminary evidence of anti-cancer activity of RH-1. [ Time Frame: Study duration ]
  4. To explore evidence of differential deoxyribonucleic acid (DNA) cross-linking and downstream phenotypic consequences of RH-1 exposure in peripheral blood mononuclear cells (PBMCs), circulating tumor cells (CTCs), and tumor biopsies. [ Time Frame: Study duration ]
  5. To explore the correlation and possible significance of germline polymorphisms in NAD(P)H:quinone oxidoreductase (NQO1) and DNA cross-linking as consequences of RH-1 exposure in PBMCs, CTCs, and tumor biopsies, as markers of anticancer activity. [ Time Frame: Study duration ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologically proven advanced solid tumors or NHL, relapsed or refractory to conventional treatment, or for which no conventional therapy exists or is considered acceptable for the patient.
  2. Tumor accessible for biopsy (required in expanded cohort of 24 patients only; optional in all other patients).
  3. At least 18 years of age.
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  5. Life expectancy ≥ 3 months.
  6. Adequate hematological, hepatic, and renal function as defined by the following: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, total bilirubin ≤ 1.5 × the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (AST/ALT ≤ 5 × ULN if documented hepatic involvement), creatinine ≤ 1.5 mg/dL or if serum creatinine is elevated then patient has a calculated creatinine clearance ≥ 50 mL/min.
  7. Toxic manifestations of previous treatment(s) have resolved, with the exceptions of ≤ Grade 2 fatigue if stable for > 2 months, ≤ Grade 2 alopecia and/or other Grade 1 toxicities, which in the opinion of the investigator should not exclude the patient (eg, palmar erythema; stable Grade 1 peripheral neuropathy).
  8. Women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Women who are postmenopausal for at least 1 year (defined as > 12 months since last menses) or are surgically sterilized do not require this test. Women of child-bearing potential and their male partners must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of RH-1. Adequate methods of contraception are double barrier methods (condoms with spermicidal jelly or foam, and diaphragm with spermicidal jelly or foam), oral, depot and injectable contraceptives, and intrauterine device (IUD). RH-1 should not be administered to women who are breast feeding.
  9. Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of RH-1.
  10. Given written informed consent (IC).

Exclusion Criteria:

  1. Active concurrent malignancy, with the exception of adequately treated carcinoma in situ of the cervix and/or basal or squamous cell carcinoma of the skin. If there is a history of prior malignancy, the patient must be disease-free for ≥ 5 years.
  2. Receipt of any investigational or conventional chemotherapy, targeted therapy, endocrine therapy, or immunotherapy within 4 weeks prior to study treatment or planned use during the course of the study. Hormonal therapy (gonadotropin-releasing hormone analog [leuprolide] for prostate cancer, somatostatin analog [octreotide] for carcinoid tumor, and anti-estrogens for breast cancer) will be allowed if the drug administration has been stable for ≥ 4 weeks.
  3. Use of any radiation therapy (RT) within 28 days prior to study treatment or planned use during the course of the study.
  4. Requires therapeutic levels of anticoagulation therapy.
  5. Failed treatment with a bone marrow transplant.
  6. Active uncontrolled infection, underlying medical condition such as patients at poor medical risk because of non-malignant systemic disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.
  7. Known to be positive for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV).
  8. Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required.
  9. Major surgery within 4 weeks of planned start of treatment.
  10. Previous exposure to RH-1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00558727

United States, Colorado
University of Colorado Health Science Center
Aurora, Colorado, United States, 80010
United States, Michigan
Hudson-Webber Cancer Research Center
Detroit, Michigan, United States, 48201
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Cancer Therapy & Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Study Chair: D. Ross Camidge, MD, PhD University of Colorado Health Science Center

Responsible Party: Spectrum Pharmaceuticals, Inc Identifier: NCT00558727     History of Changes
Other Study ID Numbers: RH-1-002
First Posted: November 15, 2007    Key Record Dates
Last Update Posted: May 10, 2013
Last Verified: May 2013

Keywords provided by Spectrum Pharmaceuticals, Inc:
Advanced Solid Tumors
Solid Tumors
Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases