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

Learn more about:
Related Clinical Trial
A Phase II Trial Evaluating the Efficacy of Cabozantinib With Patients With Refractory GCTs Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors A Study of a New Way to Treat Children With a Brain Tumor Called NGGCT Aerosolized Azacytidine as Epigenetic Priming for Bintrafusp Alfa-Mediated Immune Checkpoint Blockade in Patients With Unresectable Pulmonary Metastases From Sarcomas, Germ Cell Tumors, or Epithelial Malignancies B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults Symptom Management for YA Cancer Survivors A Study of miRNA 371 in Patients With Germ Cell Tumors Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors Aflac ST0901 CHOANOME – Sirolimus in Solid Tumors Study of Genistein in Pediatric Oncology Patients (UVA-Gen001) A Pilot RCT of the PRISM Intervention for AYAs With Cancer Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors Molecular-Guided Therapy for Childhood Cancer EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas Recombinant Human Thrombopoietin in Children Receiving Ifosfamide, Carboplatin, and Etoposide Chemotherapy MR-guided High Intensity Focused Ultrasound (HIFU) on Pediatric Solid Tumors Tandem Peripheral Blood Stem Cell (PBSC) Rescue for High Risk Solid Tumors Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors Auto Transplant for High Risk or Relapsed Solid or CNS Tumors Busulfan in Treating Children and Adolescents With Refractory CNS Cancer CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven’t Responded to Therapy ABT-751 in Treating Young Patients With Refractory Solid Tumors Temozolomide and O6-benzylguanine in Treating Children With Solid Tumors Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors Temozolomide Plus Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Malignant Glioma or Recurrent CNS or Other Solid Tumors Collecting and Storing Tissue From Young Patients With Cancer Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Everolimus in Refractory Testicular Germ Cell Cancer Studying Genes in Samples From Younger Patients With Ovarian or Testicular Sex Cord Stromal Tumors Adolescent and Young Adult Cancer Patients: Cognitive Toxicity on Survivorship (ACTS) A Phase I Study of Lyso-thermosensitive Liposomal Doxorubicin and MR-HIFU for Pediatric Refractory Solid Tumors Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors First Line TIP in Poor Prognosis TGCTs. Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy Electroacupuncture in Treating Delayed Nausea and Vomiting in Patients Receiving Chemotherapy For Newly Diagnosed Childhood Sarcoma, Neuroblastoma, Nasopharyngeal Cancer, Germ Cell Tumors, or Hodgkin Lymphoma Disulfiram and Cisplatin in Refractory TGCTs. Role of Axumin PET Scan in Germ Cell Tumor Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Gemcitabine, Paclitaxel and Oxaliplatin (GemPOx) Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors Study of the Hypomethylating Drug Guadecitabine (SGI-110) Plus Cisplatin in Relapsed Refractory Germ Cell Tumors Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors Study Evaluating the Impact of Short Message Service on Compliance With Surveillance of Patients With Germ-cell Tumors Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Aprepitant + a 5HT3 + Dexamethasone in Patients With Germ Cell Tumors Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01 Brentuximab Vedotin in Relapsed/Refractory Germ Cell Tumors Durvalumab Alone or With Tremelimumab in Refractory Germ Cell Tumors Etoposide, Carboplatin, and Bleomycin in Treating Young Patients Undergoing Surgery For Malignant Germ Cell Tumors Studying Biomarkers in Samples From Younger Patients With Malignant Germ Cell Tumor Progression Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Germ Cell Tumors Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors Conventional Dose Versus High Dose Sequential Chemotherapy for Poor Prognosis Germ Cell Tumors Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors Accelerated v’s Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumours Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors Dose Intensification Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis A Novel Single Arm Phase II Study for Relapsed Germ Cell Tumours With Poor Prognosis Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors Paclitaxel, Ifosfamide and Cisplatin (TIP) Versus Bleomycin, Etoposide and Cisplatin (BEP) for Patients With Previously Untreated Intermediate- and Poor-risk Germ Cell Tumors Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Nivolumab in Platinum Recurrent or Refractory Metastatic Germ Cell Tumors Proton Beam Radiation Therapy for Central Nervous System (CNS) Germ Cell Tumors Germ Cell Tumor and Testicular Tumor DNA Registry A Phase II Study of Sirolimus and Erlotinib in Recurrent/Refractory Germ Cell Tumors Trial of Gemcitabine, Cisplatin, and Ifosfamide in Patients With Relapsed Non-Seminomatous Germ-Cell Tumors

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

Interventional


Primary Outcome

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

Secondary Outcome

 Objective response rate (ORR)

Condition

Germ Cell Tumor

Intervention

Guadecitabine (SGI-110)

Study Arms / Comparison Groups

 Guadecitabine (SGI-110)
Description:  

Publications

* 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

Drug

Estimated Enrollment

14

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
             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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Nasser Hanna, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02429466

Organization ID

IUCRO-0508

Secondary IDs

1502729080

Responsible Party

Sponsor-Investigator

Study Sponsor

Nasser Hanna


Study Sponsor

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


Verification Date

September 2020