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

NCT02429466 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: IUCRO-05081502729080
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

Germ Cell Tumor; Testis Cancer; Testicular Cancer

Keywords

testicular germ cell tumor; ovarian germ cell tumor; platinum refractory; cisplatin; SGI110; Guadecitabine

Outcome Measures

Primary Outcomes (2)

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

  During chemotherapy (weeks 1-18)

• Maximum tolerated dose (MTD) of SGI-110 plus cisplatin

  During chemotherapy (weeks 1-18)

Secondary Outcomes (2)

• Objective response rate (ORR)

  Days 42, 84, 126, 159, and 220

• Progression free survival (PFS)

  Days 42, 84, 126, 159, and 220

Other Outcomes (2)

• Pharmacodynamic activity of SGI-110

  Day 8

• Pharmacodynamic activity of SGI-110

  Day 8

Study Arms (1)

Guadecitabine (SGI-110)

EXPERIMENTAL

Drug: Guadecitabine (SGI-110)

Interventions

Guadecitabine (SGI-110) DRUG

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.

Also known as: Guadecitabine

Guadecitabine (SGI-110)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nasser Hanna: lead

Study Sites (2)

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Testicular Germ Cell Tumor

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Study Officials

• Nasser Hanna, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 29, 2015
• Study Start: April 27, 2015
• Primary Completion: June 4, 2018
• Study Completion: February 13, 2019
• Last Updated: September 23, 2020

Record last verified: 2020-09

Locations

US (2)