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

NCT01495663 | Completed Phase 1

• 1 other identifier: DCL-10-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cancer

Keywords

refractory; relapsed; non-small cell lung cancer; triple-negative breast cancer; soft tissue sarcoma; colorectal cancer; esophageal cancer; prostate cancer; ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Determination of the recommended dose of I-131-CLR1404 in treating subjects with relapsed or refractory advanced solid malignancies

  Largest administered dose with at most a 20% dose limiting toxicity rate

  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)

Secondary Outcomes (4)

• Expansion of the safety profile of I-131-CLR1404

  Pre-infusion and 6 days after dosimetry infusion; weekly until 56 days after therapy infusion and then monthly for one year

• Expansion of the pharmacokinetic profile of I-131-CLR1404

  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

• Preliminary antitumor activity of I-131-CLR1404

  Baseline at screening, 56 days post-therapy infusion, every 2 months in follow-up period up to one year

• Tumor dosimetry of I-131-CLR1404 in a subset of subjects with non-hepatic lesions measuring at least 2 cm in one dimension

  72 hours, 6, 14, and 21 days post-therapy infusion

Study Arms (1)

Single Group

OTHER

I-131-CLR1404

Drug: I-131-CLR1404

Interventions

I-131-CLR1404 DRUG

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

Also known as: 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine

Single Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ≥ 1 lesion that qualifies as a "target lesion" based on RECIST 1.1
• Ambulatory w/ECOG performance status 0 to 2 and estimated life expectancy ≥ 4 mo.
• years or older
• Judged by Investigator to have initiative and means to be compliant with protocol and w/n 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 acceptable if clinical condition stable ≥ 1 mo. Subjects with brain metastasis requiring steroids must have been on a stable or tapering dose of corticosteroids ≥ 1 mo. prior to enrollment
• Negative serum pregnancy test w/n 24 hours of enrollment (Female subjects of childbearing potential)
• Agreement to use effective contraception method (oral contraceptives, double-barrier methods, intrauterine device, Norplant, Depo-Provera) during study and 90 days following last dose

You may not qualify if:

• 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 allowed if clinically indicated. Ongoing hormonal therapy may be continued
• Received \> 3 previous cytotoxic chemotherapy regimens
• Received \> 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 w/n 4 weeks of study start
• Extradural tumor in contact with spinal cord or tumor located where swelling in response to therapy may impinge upon spinal cord
• Other active medical condition or organ disease that may compromise 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 w/n 28 days of initiating study treatment
• Received severely marrow toxic drugs (eg nitrosoureas, mitomycin)
• Received blood transfusions or hematopoietic growth factor therapy w/n 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 (w/n 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

Sponsors & Collaborators

• Cellectar Biosciences, Inc.: lead

Study Sites (3)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007-2113, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Neoplasms; Recurrence; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Sarcoma; Colorectal Neoplasms; Esophageal Neoplasms; Prostatic Neoplasms; Ovarian Neoplasms

Interventions

CLR1404

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Glen Liu, M.D

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2011
• First Posted: December 20, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: January 1, 2014
• Last Updated: February 26, 2015

Record last verified: 2015-02

Locations

US (3)