- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02387307
A Study of rSIFN-co in Subjects With Advanced Solid Tumors (rSIFN-01)
A Phase I Open-Label, Non-Randomized, Dose-Escalation Study of rSIFN-co in Subjects With Advanced Solid Tumors and With an Expansion Cohort at Recommended Dose (RD) in Subjects With Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Hepatocellular Carcinoma or Colon Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The Dose-Escalation Cohort will consist of the Pretreatment Phase, the Treatment Phase, the Extension Phase, Discontinuation and Follow-up. The Pretreatment Phase will include a Consent and Screening Period. The Treatment Phase will consist of the Lead in Period and first 21-day cycle of treatment during which subjects will be monitored for the development of dose-limiting toxicity (DLT) following 1 week of washout. The Extension Phase will start from the start of Cycle 2 with intra-subject dose-escalation performed until discontinuation of study treatment. Upon discontinuation of study treatment, discontinuation visit assessments should occur within 7 days of treatment discontinuation or confirmation of discontinuation criteria. End of treatment information will also be collected for all subjects who discontinue treatment after completion of cycle 1 treatment. Follow-up visit/final visit evaluations will be performed 28 (±5 days) days after the last rSIFN-co administration. The decision to undergo dose-escalation to the next dose level will be based on the safety information obtained during Cycle 1.
Dose escalation in solid tumors utilizing a "3+3" design with intra-subject dose escalation. 4 dose levels of rSIFN-co are planned for determining the RD. 3-6 subjects will be assigned to each dose level and followed up for 4 weeks after starting administration in Cycle 1. Each cohort will be started after the tolerability of that dose level has been confirmed in subjects with advanced solid tumors. For subjects starting in the lower dose cohorts, intra-subject dose escalation will be allowed till grade 3/4 toxicity is encountered or highest dose level (after safety and tolerability are confirmed) TIW is reached. In order to minimize the risk of allergic reactions, the sponsor has advised a lead-in period starting from 15μg. When the tolerability of each dose level has been confirmed by the observation of no DLT among 3 subjects, escalation to the next dose level will occur.
The Expansion Cohort will be initiated at the RD. Depending on the RD, the lead in period will occur accordingly. After the lead in period, a period from Cycle 1 to the final administration will be performed as the Treatment Phase during which subjects will undergo a standardized evaluation for the safety and efficacy of rSIFN-co at the RD. If subjects are discontinued from the study treatment, discontinuation visit assessments should occur within 7 days of last rSIFN-co administration or confirmation of discontinuation criteria. End of treatment information will also be collected for all subjects who discontinue treatment after completion of cycle 1 treatment. Follow-up evaluations will be performed 28 days (±5 days) after the last rSIFN-co administration.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Singapore, Singapore, 169610
- National Cancer Centre Singapore
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
a) Histologically confirmed diagnosis of advanced solid tumors that is metastatic or unresectable and for which standard therapies (according to local practice) or palliative measures do not exist or subject decides not to receive any available treatment (dose escalation cohort) OR
b) Histologically or Cytologically diagnosis of Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Hepatocellular Carcinoma* and Colon Cancer metastatic or unrespectable and for which standard therapies (according to local practice) or palliative measures do not exist or subject decides not to receive any available treatment (dose expansion cohort) (dose expansion cohort)
* Hepatocellular Carcinoma patients may be enrolled based on radiological diagnosis instead of histological or cytological diagnosis - based on "EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma (Journal of Hepatology 56:908-943, 2012), non-invasive hepatocellular carcinoma patients should not be put under additional undue risk of liver biopsy after the diagnosis of hepatocellular carcinoma has been ascertained with clinical, laboratory and radiographic evaluation."
- Measurable disease is preferred but not mandatory for the purpose of study accrual. Evaluable disease is sufficient.
- Age > or = 21 years
- ECOG performance status < or = 2
Adequate laboratory values at the time of screening:
(For both dose escalation and expansion)
- leukocytes ≥3,000/mcL
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- haemoglobin ≥9.0 g/DL
(Dose escalation only)
- total bilirubin ≤ the upper limits of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ the upper limits of normal (ULN)
- creatinine < the upper limits of normal (ULN) OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
(Dose expansion only)
- total bilirubin ≤ 1.5 times the upper limits of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 times the upper limits of normal (ULN) or ≤ 4 times upper limits of normal (ULN) for patients with liver metastasis
- creatinine ≤1.5 times the upper limits of normal (ULN) OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above 1.5 times the institutional upper limits of normal
(For renal cell carcinoma patients)
- creatinine ≤ 1.5 times the upper limits of normal (ULN) OR creatinine clearance ≥ 40 mL/min/1.73 m2 for subjects with creatinine levels above 1.5 times the institutional upper limits of normal.
- Life expectancy > 3 months
- Agreement to be compliant to visit schedules as defined in the protocol.
- Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
- The effects of rSIFN-co on the developing human fetus are unknown. For this reason women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of r-SIFN-co administration. WOCBP must have a negative urine pregnancy test at Visit 1 (Screening).
Exclusion Criteria:
- Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to start of rSIFN-co administration or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Subjects receiving other investigational drugs within 5 times the half-life of the investigational drugs or within 4 weeks, prior to start of rSIFN-co administration.
- Subject must not have known untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, provided that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 4 weeks prior to start of rSIFN-co administration).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to interferon.
- Uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial pneumonia or psychiatric illness/social situations that would limit compliance with study requirements.
- HIV-positive subjects on combination antiretroviral therapy are ineligible because of the increased risk of lethal infections when treated with immunomodulatory therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated.
- The investigator or sub-investigator considers the subject's physique as inappropriate for investigational product treatment or any other reason(s) that may render the subjects inappropriate for participation in the trial.
- Subjects who may have autoimmune disorders, decompensated liver diseases or life-threatening neurologic diseases.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort: Dose-Escalation and Expansion
Dose-Escalation: Dose escalation in solid tumors utilizing a "3+3" design with intra-subject dose escalation. 4 dose levels of rSIFN-co are planned for determining the RD. Dose of rSIFN-co: 15, 21, 24, 27 and 30 ug. Dose-Expansion: The Expansion Cohort will be initiated at the RD. Depending on the RD, the lead in period will occur accordingly. After the lead in period, a period from Cycle 1 to the final administration will be performed as the Treatment Phase during which subjects will undergo a standardized evaluation for the safety and efficacy of rSIFN-co at the RD. Follow-up evaluations will be performed 28 days (±5 days) after the last rSIFN-co administration. |
rSIFN-co is a drug developed by Sichuan Huiyang Life Science and Technology Corporation for the treatment of solid tumors especially in non-small cell lung cancer and other tumor types.
The study comprises of 2 stages: the dose-escalation stage and dose expansion stage.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events of rSIFN-co of recombinant interferon-α administered in solid Tumor
Time Frame: Up to 12 weeks after the last treatment
|
Safety and tolerability will be determined after each cycle of treatment with SIFN-co of recombinant interferon-α, to patients via subcutaneous injection for 21 days (up to 6 cycles)
|
Up to 12 weeks after the last treatment
|
Recommended dose (RD) of rSIFN-co
Time Frame: Cycle 1 of treatment
|
3+3 design for determination of RD. 4 doses (21µg, 24µg, 27µg and 30µg) are planned for determination of RD, dose escalation will be allowed till grade 3/4 toxicity is encountered in 2 or more of the 3 or 6 subjects in first cycle of treatment cycle
|
Cycle 1 of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antitumor efficacy (Disease Control Rate), i.e. the percentage of patients, on the RD of rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Antitumor response will be evaluated based on RECIST and irRC guidelines
|
Up to 28 days after the last treatment
|
Objective response rate (ORR), i.e. the percentage of patients, on rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Subjects will be re-evaluated at end of cycle 1, completion of every even cycle treatment, Discontinuation Visit and Follow-up Visit. Confirmatory scans will be obtained within 4 to 8 weeks following initial documentation of an objective response. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]. Antitumor response based on total measurable tumor burden irRC, index and measurable new lesions are taken into account. Each subsequent tumor assessment, the SPD of the index lesions and of new, measurable lesions (≥5 × 5 mm; up to 5 new lesions per organ: 5 new cutaneous lesions and 10 visceral lesions) are added together to provide the total tumor burden, the objective is to determine response rate (ORR), progression-free survival (PFS),and time to progression (TTP) status on rSIFN-co. |
Up to 28 days after the last treatment
|
Progression-free survival (PFS) time (days) on rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Subjects will be re-evaluated at end of cycle 1, completion of every even cycle treatment, Discontinuation Visit and Follow-up Visit. Confirmatory scans will be obtained within 4 to 8 weeks following initial documentation of an objective response. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]. Antitumor response based on total measurable tumor burden irRC, index and measurable new lesions are taken into account. Each subsequent tumor assessment, the SPD of the index lesions and of new, measurable lesions (≥5 × 5 mm; up to 5 new lesions per organ: 5 new cutaneous lesions and 10 visceral lesions) are added together to provide the total tumor burden, the objective is to determine response rate (ORR), progression-free survival (PFS),and time to progression (TTP) status on rSIFN-co. |
Up to 28 days after the last treatment
|
Time to progression (TTP) status (days) on rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Subjects will be re-evaluated at end of cycle 1, completion of every even cycle treatment, Discontinuation Visit and Follow-up Visit. Confirmatory scans will be obtained within 4 to 8 weeks following initial documentation of an objective response. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]. Antitumor response based on total measurable tumor burden irRC, index and measurable new lesions are taken into account. Each subsequent tumor assessment, the SPD of the index lesions and of new, measurable lesions (≥5 × 5 mm; up to 5 new lesions per organ: 5 new cutaneous lesions and 10 visceral lesions) are added together to provide the total tumor burden, the objective is to determine response rate (ORR), progression-free survival (PFS),and time to progression (TTP) status on rSIFN-co. |
Up to 28 days after the last treatment
|
FDG-PET response (lesion size) before and after administration of rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
CT and SUV values used to determine lesion size will be evaluated and studied to understand the change of CT value& SUV value before and after treatment.
|
Up to 28 days after the last treatment
|
FDG-PET response (lesion volume) before and after administration of rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
CT and SUV values used to determine lesion volume will be evaluated and studied to understand the change of CT value& SUV value before and after treatment.
|
Up to 28 days after the last treatment
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in subject cytokine profiles (pg/ml) before and after treatment
Time Frame: Up to 28 days after the last treatment
|
The cytokine data is an experimental observation and not used for therapeutic effect evaluation. if possible, to evaluate the correlation between these cytokine changes and study drugs.
|
Up to 28 days after the last treatment
|
Evaluation of elected tumor repressive and enhancing genes (counts of genes such as microRNA-92a, microRNA-92b) before and after administration of rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Pre- and post-dose samples will be collected for additional cell signaling assays to evaluate selected tumor repressive and enhancing genes (such as microRNA-92a, microRNA-92b) as well as levels of 2'5'-oligoadenylate synthetase.
|
Up to 28 days after the last treatment
|
Evaluation of levels (counts) of 2'5'-oligoadenylate synthetase, before and after administration of rSIFN-co
Time Frame: Up to 28 days after the last treatment
|
Pre- and post-dose samples will be collected for additional cell signaling assays to evaluate selected tumor repressive and enhancing genes (such as microRNA-92a, microRNA-92b) as well as levels of 2'5'-oligoadenylate synthetase.
|
Up to 28 days after the last treatment
|
Collaborators and Investigators
Investigators
- Principal Investigator: David Wai Meng TAI, National Cancer Center Singapore
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Liver Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Kidney Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Liver Neoplasms
- Intestinal Neoplasms
- Lung Neoplasms
- Colorectal Neoplasms
- Neuroendocrine Tumors
- Nevi and Melanomas
- Carcinoma, Renal Cell
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Carcinoma, Hepatocellular
- Melanoma
- Colonic Neoplasms
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Interferons
Other Study ID Numbers
- rSIFN-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma
-
H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
-
National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
-
Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
Clinical Trials on rSIFN-co
-
Sichuan Huiyang Life Science and Technology CorporationActive, not recruitingCOVID-19 | SARS-CoV-2 InfectionPhilippines
-
Sichuan Huiyang Life Science and Technology CorporationMedelis Inc.Active, not recruitingMalignancies Including Melanoma, Kidney, Lung, Colorectal, Prostate, Neuroendocrine TumorUnited States
-
Haukeland University HospitalCompleted
-
Boston Medical CenterNot yet recruitingSubstance Use Disorders | Mental Health IssueUnited States
-
Johns Hopkins UniversityNational Institute of Nursing Research (NINR)Active, not recruitingQuality of Life | Multimorbidity | Symptom ManagementUnited States
-
Federal University of Minas GeraisCompletedAttention Deficit and Disruptive Behavior Disorders | Motor Skills DisordersBrazil
-
Memorial Sloan Kettering Cancer CenterTerminated
-
PXL University CollegeRecruitingExercise | Older Adults | Mobile ApplicationBelgium
-
IpasTerminatedAbortion, Induced | Abortion, IncompleteMexico, South Africa
-
Children's Hospital of PhiladelphiaChildren's Anesthesiology Associates, Ltd.CompletedScoliosis | Spinal FusionUnited States