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Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02429466
Recruitment Status : Active, not recruiting
First Posted : April 29, 2015
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
Nasser Hanna, Indiana University School of Medicine

Tracking Information
First Submitted Date  ICMJE April 14, 2015
First Posted Date  ICMJE April 29, 2015
Last Update Posted Date December 12, 2019
Actual Study Start Date  ICMJE April 27, 2015
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2018)
  • Dose limiting toxicity (DLT) of guadecitabine (SGI-110) plus cisplatin [ Time Frame: During chemotherapy (weeks 1-18) ]
  • Maximum tolerated dose (MTD) of SGI-110 plus cisplatin [ Time Frame: During chemotherapy (weeks 1-18) ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2015)
  • Dose limiting toxicity (DLT) of SGI-110 plus cisplatin [ Time Frame: During chemotherapy (weeks 1-18) ]
  • Maximum tolerated dose (MTD) of SGI-110 plus cisplatin [ Time Frame: During chemotherapy (weeks 1-18) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2015)
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 24, 2015)
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors
Official Title  ICMJE Phase I Study of the Hypomethylating Drug SGI-110 Plus Cisplatin in Relapsed Refractory Germ Cell Tumors
Brief Summary This is an open-label, single arm, Phase I dose escalation study in subjects with refractory germ cell tumor (rGCT). This phase I will evaluate the safety and efficacy of SGI-110 in combination with cisplatin in subjects with rGCT. The primary objective is to determine the maximum tolerated dose (MTD) of SGI-110 to be used prior to cisplatin. A total of 15 subjects will be enrolled in this study at the Indiana University Simon Cancer Center.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Germ Cell Tumor
  • Testis Cancer
  • Testicular Cancer
Intervention  ICMJE Drug: 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 Name: Guadecitabine
Study Arms  ICMJE Experimental: Guadecitabine (SGI-110)
Intervention: Drug: Guadecitabine (SGI-110)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 24, 2015)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date December 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. ≥ 18 years old at the time of informed consent
  2. Written informed consent and HIPAA authorization for release of personal health information.
  3. 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.
  4. Subjects with histologically or serologically confirmed diagnosis of recurrent germ cell tumor.
  5. Subjects who have platinum-resistant disease. There is no limit on the number of prior treatment regimens.
  6. Subjects must have had prior high dose chemotherapy (HDCT) treatment when indicated.
  7. 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.

  8. Subjects with ECOG performance status of 0-2.
  9. Subjects must be at least 3 weeks from last chemotherapy.
  10. 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.
  11. 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:

  1. 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.

  2. Treatment with any investigational agent within 30 days prior to registration for protocol therapy.
  3. Concurrent participation in a clinical trial which involves another investigational agent.
  4. Subjects with Grade 2 or greater neuropathy.
  5. 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.
  6. Pregnancy or breast-feeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02429466
Other Study ID Numbers  ICMJE IUCRO-0508
1502729080 ( Other Identifier: Indiana University IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nasser Hanna, Indiana University School of Medicine
Study Sponsor  ICMJE Nasser Hanna
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nasser Hanna, MD Indiana University School of Medicine
PRS Account Indiana University
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP