Study of RM-1929 and Photoimmunotherapy in Patients With Recurrent Head and Neck Cancer
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|ClinicalTrials.gov Identifier: NCT02422979|
Recruitment Status : Active, not recruiting
First Posted : April 22, 2015
Last Update Posted : June 19, 2018
This is a two-part clinical study of patients with recurrent Head and Neck Cancer (HNC), who in the opinion of their physician, cannot be satisfactorily treated with surgery, radiation or platinum chemotherapy. The purpose of the study is to determine the safety and anti-cancer activity of various doses and repeated cycles of the experimental treatment using the study drug RM-1929 and fixed amounts of red light applied at the tumor site to activate the pharmacodynamics of the drug.
The part 1 of the study has been completed and consisted in a single cycle, 3+3 dose escalation safety study of the experimental drug RM-1929 using a fixed amount of 690 nm red light. The part 1 was designed to determine the safety of the treatment as set by the maximal feasible dose or the maximal tolerable dose of RM-1929. From the part 1 results, the maximal feasible dose of RM-1929 was determined.
The part 2 of the study is currently ongoing and it is evaluating the safety and anticancer efficacy of up to four repeated treatments of Photoimmunotherapy with RM-1929 at the maximal feasible dose of RM-1929 activated with a fixed amount of red light.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Head and Neck Cancer||Drug: RM-1929 Device: Photoimmunotherapy||Phase 1 Phase 2|
Photoimmunotherapy (PIT) is a new cancer targeted technology invented at the National Cancer Institute, USA. This clinical study evaluates the treatment of the experimental drug RM-1929 with Photoimmunotherapy (PIT).
The experimental drug, RM-1929, is a parental formulation consisting of a chemical conjugate of the dye IR700 with the FDA approved antibody, Erbitux® (Cetuximab), that targets EGFR receptors (EGFR is a cancer expressed protein, a cancer antigen). EGFR is highly expressed in squamous cell carcinomas of the head and neck (HNSCC). It is expected that systemic administration of RM-1929 will lead to tumor accumulation and binding to EGFR expressed at cancer cells. It is expected that treatment with RM-1929 and Photoimmunotherapy can lead to the selective destruction of the HNSCC cancer cells and provide an effective therapy to manage the disease.
The treatment using RM-1929 with Photoimmunotherapy requires two steps:
(i) the administration by infusion of the drug RM-1929 targeting the cancer protein EGFR
(ii) the illumination of the tumor with red light (690 nm) using sufficient energy to activate the drug and induce cancer cell killing.
Light illumination is applied at 24 h post drug infusion to enable sufficient time for the drug to distribute in the tumor after administration. Cell killing occurs only at cancer cells expressing the protein EGFR that is bound to the drug RM-1929. The requirement of binding of the drug to EGFR of cancer cells enables the selective destruction of cancer cells with minimum damage of healthy tissue surrounding the tumor cells. Preclinical pharmacology demonstrated that light-induced activation of RM-1929 elicits rapid tumor destruction of human cancer xenografts implanted in mice and that the treatment is cancer specific.
The Part 1 study has been completed and consisted of a single cycle 3+3 dose escalation study of RM-1929 to determine the safety of the treatment and the maximal feasible dose of RM-1929. From the part 1 of this study, the maximal feasible dose for treatment with RM-1929 was selected. The currently ongoing Part 2 of the clinical study is evaluating the safety and anti-cancer activity of up to 4 repeat treatment cycles of Photoimmunotherapy with RM-1929.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2a Multicenter, Open-Label, Dose-Escalation, Combination Study of RM-1929 and Photoimmunotherapy in Patients With Recurrent Head and Neck Cancer, Who in the Opinion of Their Physician, Cannot Be Satisfactorily Treated With Surgery, Radiation or Platinum Chemotherapy|
|Actual Study Start Date :||June 2015|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||September 2018|
Experimental: Combination Study: RM-1929 & Photoimmunotherapy
RM-1929 & Photoimmunotherapy
Dose-escalation, fixed low fluency light application study to determine the drug dose that can be safely given to saturate the epidermal growth factor receptor (EGFR) at the tumor
Light dose-escalation, fixed drug dosing infusion study to determine the optimal light application, in combination with the Part I drug dose, needed to achieve clinical response with an acceptable safety profile.
- Part I: Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) of RM-1929, whichever is lowest [ Time Frame: 1 month ]Determine the MTD or MFD of RM-1929
- Part I: Adverse Event profile for each drug dose of RM-1929 [ Time Frame: 1 month ]Assessment of safety of the combination of drug dose with low energy localized light irradiation
- Part I: Photosafety (sunburn) Testing [ Time Frame: 1 month ]Determination of skin Minimal Erythema Dose (MED) following infusion of RM-1929
- Part II: Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) of a fixed drug dose with fixed light dose [ Time Frame: 1 month ]Determination of MTD or MFD of fixed drug dose with fixed light dose
- Part II: Safety with repeat dosing [ Time Frame: 2 years or until death ]Safety parameters associated with repeat dosing
- Part I: Tumor response [ Time Frame: 2 months ]Document tumor response using response assessment in solid tumors version 1.1 (RECIST 1.1), including additional assessment of target lesion volumetrics
- Part 1: Tumor reduction/necrosis [ Time Frame: 2 month ]Document tumor reduction/necrosis using Choi criteria
- Part I: Pharmacokinetics of RM-1929 and for both RM-1929 and unconjugated IRDye 700DX (Cmax, T 1/2, AUC, CL and Vss) [ Time Frame: 1 month ]
- Part I: Immunogenic response to RM-1929 [ Time Frame: 2 month ]To assess antibodies to RM-1929 or cetuximab
- Part II: Tumor Response [ Time Frame: 2 months ]Assessed using RECIST 1.1
- Part II: Tumor Reduction [ Time Frame: 2 months ]Evaluation by CT scans, clinical measurement, photographs, biopsies, symptom relief and ECOG performance
- Part II: Immunogenic response to RM-1929 [ Time Frame: 2 months ]To assess antibodies to RM-1929 or cetuximab
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 ClinicalTrials.gov identifier (NCT number): NCT02422979
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Colorado|
|Centura Health Research Center|
|Denver, Colorado, United States, 80210|
|United States, Illinois|
|Rush University Cancer Center|
|Chicago, Illinois, United States, 60612|
|United States, Minnesota|
|Virginia Piper Cancer Institute, part of Allina Health System|
|Minneapolis, Minnesota, United States, 55407|
|United States, Oklahoma|
|University of Oklahoma Stephenson Cancer Center|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|