A Japanese Trial of TH-302 in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

NCT02255110 | Terminated Phase 2 Results

• 1 other identifier: EMR200592-008
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 2, single-arm, Japanese multicenter trial to evaluate the safety, tolerability, and efficacy of TH-302 in combination with doxorubicin in subjects with locally advanced unresectable or metastatic soft tissue sarcoma (STS).

Conditions

Soft Tissue Sarcoma

Keywords

Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma; TH-302; Doxorubicin; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) by Independent Central Review (Phase II Treatment Period)

  PFS was planned to assess as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progressive Disease is defined as at least a 20 percent (%) increase in the Sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  From first dose of study drug administration until PD or death, evaluated at 6 months

Secondary Outcomes (8)

• Progression Free Survival (PFS) by Investigator Review (Phase II Treatment Period)

  From first dose of study drug administration until PD or death, evaluated at 6 months

• Progression-free Survival (PFS) by Investigator and Independent Central Review (Phase II Treatment Period)

  From first dose of study drug administration until PD or death, evaluated at 3 months and 9 months

• Progression-free Survival (PFS) (Phase II Treatment Period)

  From first dose of study drug administration until PD or death, assessed up to 12 months

• Best Overall Response (BOR) by Independent Central Review (Phase II Treatment Period)

  From first dose of study drug administration until PD or death, assessed up to 12 months

• Best Overall Response (BOR) by Investigator (Phase II Treatment Period)

  From first dose of study drug administration until PD or death, assessed up to 12 months

Study Arms (1)

TH-302 and doxorubicin

EXPERIMENTAL

Drug: TH-302; Drug: Doxorubicin

Interventions

TH-302 DRUG

TH-302 will be administered at a dose of 300 milligram per square meter (mg/m\^2) by intravenous infusion over 30 minutes on Days 1 and 8 of every 21-day cycle until the evidence of significant treatment-related toxicity or progressive disease.

TH-302 and doxorubicin

Doxorubicin DRUG

Doxorubicin will be administered at a dose of 75 mg/m\^2 by intravenous injection (over at least 5 minutes) or by intravenous infusion over 6-96 hours on Day 1 of every 21-day cycle starting 2 to 4 hours after completion of TH-302 administration until the evidence of significant treatment-related toxicity or progressive disease.

TH-302 and doxorubicin

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female Japanese subjects greater than or equal to (\>=) 15 years of age
• Able to understand the purposes and risks of the trial and has signed or, if appropriate, the subject's parent or legal guardian has signed a written informed consent form approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC)
• Pathologically confirmed diagnosis of STS of the histopathologic types as specified in the protocol
• Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate
• Recovered from reversible toxicities of prior therapy
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 3 months
• Acceptable liver function, renal function, hematologic status (without growth factor support for neutropenia or transfusion dependency), and cardiac function as specified in the protocol
• All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception (surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an intrauterine device, intrauterine device \[IUD\]) with their partner from entry into the trial through 6 months after the last dose. Post-menopausal women must meet the criteria of 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels greater than (\>) 35 international units per liter (IU/L)

You may not qualify if:

• Low grade tumors according to standard grading systems (for example, American Joint Committee on Cancer \[AJCC\] Grade 1 and 2 or Fédération Nationale des Centres de Lutte Contre le Cancer \[FNCLCC\] Grade 1)
• Prior systemic therapy for advanced or metastatic STS (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted)
• Prior STS therapy with ifosfamide or cyclophosphamide or other nitrogen mustards; prior systemic therapy with an anthracycline or anthracenedione; or prior mediastinal/cardiac radiotherapy
• Current use of drugs with known cardiotoxicity or known interactions with doxorubicin
• Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 4 weeks prior to trial entry (6 weeks for nitrosoureas or mitomycin C).
• Significant cardiac dysfunction precluding treatment with doxorubicin as specified in the protocol
• Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last year
• Known brain metastases (unless previously treated and well controlled for a period of \>=3 months before screening)
• Previously diagnosed malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years before screening
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Prior therapy with a hypoxic cytotoxin
• Subjects who participated in an investigational drug or device trial within 28 days prior to trial entry
• Known infection with human immunodeficiency virus (HIV) or active infection with hepatitis B or hepatitis C

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (2)

Research Site

Kashiwa, Japan

Location

Research Site

Tokyo, Japan

Location

MeSH Terms

Conditions

Sarcoma

Interventions

TH 302; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

This study was terminated early following the discontinuation of TH-302 clinical development program. Only 6 subjects were enrolled and treated in the Safety Run-In Phase; thus, the statistical analyses are limited to the Safety Run-In Phase.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Co., Ltd., Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Study Start: December 10, 2014
• Primary Completion: January 12, 2016
• Study Completion: January 12, 2016
• Last Updated: December 14, 2018
• Results First Posted: December 14, 2018

Record last verified: 2018-07

Locations

JP (2)