- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02429466
Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors
Phase I Study of the Hypomethylating Drug SGI-110 Plus Cisplatin in Relapsed Refractory Germ Cell Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary Objective:
To assess the safety and toxicity of guadecitabine (SGI-110) plus cisplatin including the dose limiting toxicity (DLT) and to determine the Maximum tolerated dose (MTD)
Secondary Objective:
To assess the efficacy of guadecitabine (SGI-110) to resume sensitivity to cisplatin in refractory GCT
Correlative Objective:
To evaluate the pharmacodynamic activity of guadecitabine (SGI-110) Evaluate miRNA biomarkers in serum on day 1 of cycles 1-6
Intervention and Mode of Delivery: Guadecitabine (SGI-110) will be given subcutaneously, daily, 30 mg/m2 on days (1-5) followed by cisplatin 100mg/m2 on day 8 every 4 weeks.
Duration of Intervention and Evaluation:
Treatment will be continued for a maximum of 6 cycles or until disease progression or unacceptable toxicity whichever occurs first. Subjects who are responding to therapy without major toxicty would be allowed to continue on single agent guadecitabine (SGI-110) at the MTD after 4-6 cycles of the combination therapy until disease progression. Subjects will be followed after the last cycle every 2 months for the 1st year, and every 4 months thereafter until death (expected overall survival less than 12 months).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Cancer Center
-
Indianapolis, Indiana, United States, 46202
- Indiana University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥ 18 years old at the time of informed consent
- Written informed consent and HIPAA authorization for release of personal health information.
- Subjects who are willing and able to comply with the protocol and study procedures including willingness to undergo tumor biopsy for tumor cells before therapy at Cycle 1, Day 1, and Day 8 (before cisplatin dose) if this is clinically and safely feasible to do so.
- Subjects with histologically or serologically confirmed diagnosis of recurrent germ cell tumor.
- Subjects who have platinum-resistant disease. There is no limit on the number of prior treatment regimens.
- Subjects must have had prior high dose chemotherapy (HDCT) treatment when indicated.
Subjects who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or elevated Tumor markers (hCG or AFP).
Note: patients without measurable disease are allowed on the study as long as they have clearly rising tumor markers and they will be exempt from biopsy.
- Subjects with ECOG performance status of 0-2.
- Subjects must be at least 3 weeks from last chemotherapy.
Females of childbearing potential must not be pregnant or breast-feeding. Male and female patients of reproductive potential must agree to use two forms of highly effective contraception from the screening visit through 30 days after the last dose of study drug. Acceptable forms of effective contraception include:
- Oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
- True abstinence: When this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.] Pregnancy tests for females of childbearing potential are required; must be serum at screening and the post treatment safety assessment visit. A positive urine pregnancy test must be confirmed by a serum pregnancy test and a pelvic US since some NSGCT may secrete beta-hCG and cause a false positive pregnancy. A pelvic US does not need to be repeated with each cycle unless the treating physician thinks it is necessary to do so.
The following laboratory values must be obtained within 14 days prior to registration for protocol therapy.
- Absolute neutrophil count ≥ 1500 cells/mm3
- Hemoglobin (Hgb) ≥ 8 g/dL
- Platelets count ≥ 100,000 cells/mm3
- Serum creatinine levels ≤ 1.5 mg/dl and calculated (by Cockcroft-Gault formula) or measured creatinine clearance ≥ 50 mL/min
- Bilirubin ≤ 2 x ULN
- Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN
- Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN
Exclusion Criteria:
Active central nervous system (CNS) metastases. Subjects with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician.
NOTE: A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic.
- Treatment with any investigational agent within 30 days prior to registration for protocol therapy.
- Concurrent participation in a clinical trial which involves another investigational agent.
- Subjects with Grade 2 or greater neuropathy.
- Subjects with a life-threatening illness, medical condition or organ system dysfunction, or other reasons which, in the Investigator's opinion, could compromise the subject's safety, interfere with or compromise the integrity of the study outcomes including incomplete recovery from the acute effects from any prior anti-neoplastic therapy.
- Pregnancy or breast-feeding.
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: Guadecitabine (SGI-110)
|
SGI-110 will be given subcutaneously, daily, 30 mg/m2 on days (1-5) followed by cisplatin 100mg/m2 on day 8 every 4 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose limiting toxicity (DLT) of guadecitabine (SGI-110) plus cisplatin
Time Frame: During chemotherapy (weeks 1-18)
|
During chemotherapy (weeks 1-18)
|
Maximum tolerated dose (MTD) of SGI-110 plus cisplatin
Time Frame: During chemotherapy (weeks 1-18)
|
During chemotherapy (weeks 1-18)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Days 42, 84, 126, 159, and 220
|
To evaluate Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST)
|
Days 42, 84, 126, 159, and 220
|
Progression free survival (PFS)
Time Frame: Days 42, 84, 126, 159, and 220
|
The investigators will look at the duration between starting the therapy until progression of disease of subjects on this study
|
Days 42, 84, 126, 159, and 220
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacodynamic activity of SGI-110
Time Frame: Day 8
|
Blood collection to measure change in peripheral blood mononuclear cells (PBMCs), global DNA and selected genes, and expression of DNMT levels
|
Day 8
|
Pharmacodynamic activity of SGI-110
Time Frame: Day 8
|
Tumor tissue collection to measure change in global DNA and selected tumor genes, and expression of DNMT levels
|
Day 8
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Nasser Hanna, MD, Indiana University School of Medicine
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
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Endocrine System Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Genital Neoplasms, Male
- Testicular Diseases
- Neoplasms, Germ Cell and Embryonal
- Testicular Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Azacitidine
- Guadecitabine
Other Study ID Numbers
- IUCRO-0508
- 1502729080 (Other Identifier: Indiana University IRB)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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