Dose Escalation Study of I-131-CLR1404 in Subjects With Cancer That Does Not Respond to Treatment or Has Returned

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01495663
First received: December 16, 2011
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine the recommended dose of I-131-CLR1404, a radiolabeled therapy compound, for treating subjects with cancer that does not respond to treatment or has returned. The identified recommended dose in this study will be used as the optimal dose of I-131-CLR1404 in subsequent clinical trials conducted for later phase clinical development.

Subjects who meet study entry criteria will receive I-131-CLR1404. For each subject, the study will be conducted in two phases, dosimetric and therapy. In the dosimetric phase, subjects will receive one 5 mCi dose of the study drug and undergo whole body imaging on on the day of infusion and on post-infusion days 1, 2, 3, and 6 for assessment of biodistribution of I-131-CLR1404. If normal and expected biodistribution are demonstrated, the subject will begin the therapy phase. In the therapy phase, the first cohort of subjects will receive a dose of 12.5 mCi/m2. Dose escalation in subsequent cohorts will initially be in increments of 12.5 mCi/m2. Subjects will be followed and observed for unacceptable toxicity through 56 days after the therapy dose infusion with follow-up for up to one year.

All subjects will be prescribed thyroid protection medication to be taken 24 hours prior to injection of the dosimetric dose, and continuing for 14 days after the administration of the therapy dose.


Condition Intervention Phase
Cancer
Drug: I-131-CLR1404
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Multi-Center, Open-Label, Dose Escalation Study of I-131-CLR1404 in Subjects With Relapsed or Refractory Advanced Solid Malignancies

Resource links provided by NLM:


Further study details as provided by Cellectar Biosciences, Inc.:

Primary Outcome Measures:
  • Determination of the recommended dose of I-131-CLR1404 in treating subjects with relapsed or refractory advanced solid malignancies [ Time Frame: Until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (56 days after all subjects in cohort have received therapy infusion) ] [ Designated as safety issue: Yes ]
    Largest administered dose with at most a 20% dose limiting toxicity rate


Secondary Outcome Measures:
  • Expansion of the safety profile of I-131-CLR1404 [ Time Frame: Pre-infusion and 6 days after dosimetry infusion; weekly until 56 days after therapy infusion and then monthly for one year ] [ Designated as safety issue: Yes ]
    Assesment by physical examination, vital signs, ECG, laboratory changes over time, and adverse events

  • Expansion of the pharmacokinetic profile of I-131-CLR1404 [ Time Frame: Pre-infusion and 144 hours post-dosimetry infusion; pre-infusion, 5, 15, 60 minutes, 5, 24, 72 hours, 6, 14, 21, 28, 35, 42, 49 and 56 days post-therapy infusion ] [ Designated as safety issue: No ]

    Determination of the following pharmacokinetic parameters of I-131-CLR1404:

    • Area under the plasma concentration versus time curve (AUC)
    • Maximum (peak) plasma concentration (Cmax)
    • Time required to reduce the plasma concentration to one half its initial value (t1/2)
    • Volume of distribution (Vd)
    • Clearance of the drug from plasma (Cl)

  • Preliminary antitumor activity of I-131-CLR1404 [ Time Frame: Baseline at screening, 56 days post-therapy infusion, every 2 months in follow-up period up to one year ] [ Designated as safety issue: No ]
    CT imaging (response and progression will be evaluated using RECIST 1.1) and tumor marker evaluation in subjects with applicable tumors (performed at screening, 28 and 56 days post-therapy infusion)

  • Tumor dosimetry of I-131-CLR1404 in a subset of subjects with non-hepatic lesions measuring at least 2 cm in one dimension [ Time Frame: 72 hours, 6, 14, and 21 days post-therapy infusion ] [ Designated as safety issue: No ]
    SPECT or SPECT/CT


Enrollment: 12
Study Start Date: December 2011
Study Completion Date: January 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single Group Drug: I-131-CLR1404

Description:

  • Dosimetry: IV, 5 mCi, single dose, 6-day duration
  • Therapy: IV, starting dose level of 12.5 mCi/m2, single dose, 56-day duration with follow up to one year
Other Name: 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or refractory advanced solid malignancy or choice not to pursue standard treatment. Tumor types allowed: non-small cell lung, triple negative breast, soft tissue sarcoma, colorectal, gastric, esophageal, prostate, ovarian cancer
  • At least one lesion that qualifies as a "target lesion" based on RECIST 1.1
  • Ambulatory with ECOG performance status of 0 to 2 and an estimated life expectancy of at least 4 months
  • 18 years of age or older
  • Judged by Investigator to have initiative and means to be compliant with protocol and within geographical proximity to make required study visits
  • Ability to read, understand and provide written informed consent for initiation of any study related procedures (subject or legal representative)
  • Brain metastasis are acceptable if clinical condition has been stable for at least 1 month. Subjects with brain metastasis who require steroids must have been on a stable or tapering dose of corticosteroids for at least 1 month prior to enrollment
  • Negative serum pregnancy test within 24 hours of enrollment (Female subjects of childbearing potential)
  • Agreement to use an effective method of contraception (oral contraceptives, double-barrier methods such as condom and diaphragm, intrauterine device, Norplant, Depo-Provera) during the study and for 90 days following last dose of study drug

Exclusion Criteria:

  • Subject or physician plans concomitant chemotherapy, therapeutic radiation and/or biological treatment for cancer including immunotherapy while on study. Localized palliative radiation therapy for bone pain is allowed during study period if clinically indicated. Ongoing hormonal therapy may be continued
  • Received more than three previous cytotoxic chemotherapy regimens
  • Received more than 25% of total bone marrow irradiated, total body or hemi-body irradiation or prior radioisotope therapy (except for benign thyroid disease)
  • Diffuse lung disease or interstitial spread of carcinoma
  • Prior radiation therapy or chemotherapy within 4 weeks of start of study
  • Extradural tumor in contact with spinal cord or tumor located where swelling in response to therapy may impinge upon spinal cord
  • Another active medical condition(s) or organ disease(s) that may compromise subject safety or interfere with safety and/or outcome evaluation of study drug
  • Laboratory abnormalities, including but not limited to: WBC < 3000/uL, Absolute neutrophil count < 1500/uL, Platelets < 150,000/uL, Hemoglobin ≤ 9.0 gm/dL, Total bilirubin > 1.5 x upper limit of normal for age, SGOT or SGPT > 3 x upper limit of normal for age if no liver metastases or > 5 x upper limit of normal for age in the presence of liver metastases, Serum creatinine > 1.5 x upper limit of normal for age, INR ≥ 2.0, 2+ proteinuria or casts indicative of intrinsic renal disease
  • Treatment with investigational drug, investigational biologic, or investigational therapeutic device within 28 days of initiating study treatment
  • Received severely marrow toxic drugs (e.g. nitrosoureas, mitomycin)
  • Received blood transfusions or hematopoietic growth factor therapy within 30 days of study start
  • Received prior stem cell transplantation
  • Clinically significant cardiac co-morbidities including congestive heart failure (New York Heart Association class III-IV heart disease), left ventricular ejection fraction < 40%, unstable angina pectoris, serious cardiac arrhythmia requiring medication or pacemaker, myocardial infarction within past 6 months
  • Concurrent or recent (within 1 month) use of thrombolytic agents, or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters). Therapy with low-molecular weight heparin is acceptable as long as INR < 2.0
  • Uncontrolled hypertension as defined by systolic blood pressure > 150 mm/Hg, diastolic blood pressure > 100 mm/Hg or uncontrolled diabetes that would compromise subject safety or interfere with safety and/or outcome evaluation of study drug
  • Grade II-IV peripheral vascular disease or peripheral vascular surgery within past year
  • Major surgery within 4 weeks of enrollment
  • Poor venous access and unable to receive study drug into a peripheral venous catheter
  • Significant traumatic injury within past 4 weeks
  • Ongoing or active infection requiring antibiotics or with fever >38.1º C (>101º F) within 3 days of first scheduled day of dosing
  • Receiving concurrent hemodialysis or peritoneal dialysis
  • Known positive for HIV, Hepatitis C (active, previously treated or both), or is Hepatitis B core antigen positive
  • Pregnant or lactating
  • Hospitalized
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495663

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, District of Columbia
Georgetown University Hospital
Washington, DC, District of Columbia, United States, 20007-2113
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Cellectar Biosciences, Inc.
Investigators
Principal Investigator: Glen Liu, M.D University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: Cellectar Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01495663     History of Changes
Other Study ID Numbers: DCL-10-001
Study First Received: December 16, 2011
Last Updated: May 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cellectar Biosciences, Inc.:
refractory
relapsed
non-small cell lung cancer
triple-negative breast cancer
soft tissue sarcoma
colorectal cancer
esophageal cancer
prostate cancer
ovarian cancer

ClinicalTrials.gov processed this record on July 26, 2014