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

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Brief Title

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

Official Title

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 Phase

Phase 1

Study Type


Primary Outcome

Dose limiting toxicity (DLT) of guadecitabine (SGI-110) plus cisplatin

Secondary Outcome

 Objective response rate (ORR)


Germ Cell Tumor


Guadecitabine (SGI-110)

Study Arms / Comparison Groups

 Guadecitabine (SGI-110)


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 27, 2015

Completion Date

February 13, 2019

Primary Completion Date

June 4, 2018

Eligibility Criteria

        Inclusion Criteria:

          1. ≥ 18 years old at the time of informed consent

          2. Written informed consent and HIPAA authorization for release of personal health

          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

          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

          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

          6. Pregnancy or breast-feeding.




18 Years - N/A

Accepts Healthy Volunteers



Nasser Hanna, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Nasser Hanna

Study Sponsor

Nasser Hanna, MD, Principal Investigator, Indiana University School of Medicine

Verification Date

September 2020