Phase IIa Dose-Expansion and Biomarker Study of OPB-111077

NCT03158324 | Unknown Phase 2

• 1 other identifier: 2016/01181
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IIa open-label, non-randomized dose-expansion study of OPB-111077 in patients with advanced, treatment refractory cancers who have biopsy-amenable lesions at study entry.

Conditions

NPC; Refractory Tumor

Outcome Measures

Primary Outcomes (1)

• Objective response rates

  This will be calculated as the percentage of evaluable patients achieving complete and partial response with OPB-111077 treatment, according to the RECIST 1.1 criteria

  3 years

Secondary Outcomes (3)

• Metabolic response rates

  3 years

• Progression free survival

  3 years

• Haematologic and non-haematologic toxicities (all grades)

  3 years

Study Arms (1)

Advanced refractory solid tumors

EXPERIMENTAL

Patients with advanced refractory solid tumors will be enrolled.

Drug: OPB-111077

Interventions

OPB-111077 DRUG

Receive 600 mg of OPB-111077 on a 4 days-on, 3 days-off per week in 28-day cycles till disease progression or intolerable toxicity

Advanced refractory solid tumors

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, locally recurrent or metastatic solid tumors, who have failed standard treatment
• Subjects with NPC will be eligible as long as they have received prior platinum therapy
• Subjects with other types of solid tumors will be eligible if: i) their archival tumor sample shows over-expression oxidative phosphorylation markers e.g., PGC-1α/ SIRT1 or ii) they have oncogene-addicted cancers (e.g., EGFR mutation-positive NSCLC, EML4-ALK fusion NSCLC, BRAF-mutant melanomas, GIST, RET-driven thyroid cancers) which have become resistant to primary TKI therapy
• All subjects must have at least one tumour lesion (primary or metastatic) that is suitable for free-hand or image-guided biopsy at baseline.
• Age ≥ 21 years, Eastern Cooperative Oncology Group (ECOG) performance status \< 1
• Adequate bone marrow, liver and renal function
• Baseline serum lactate ¬\<3mmol/l
• Capable of swallowing tablets
• Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
• Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.

You may not qualify if:

• Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 3 weeks of starting investigational medicinal product (IMP).
• Use of any prohibited medications (CYP3A4 inhibitors and inducers) or medications which may predispose to lactic acidosis (e.g., metformin, nucleoside analogue reverse within 1 week prior to start of study drug administration
• Pregnancy or breastfeeding.
• Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study medication, and a negative result must be documented before start of study medication. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) upon signing the informed consent form until at least 3 months after the last study drug administration.
• Known or suspected allergy to the investigational agent or any agent given in association with this study.
• Concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis \& T1) or any cancer curatively treated less than 3 years prior to study entry.
• Interstitial lung disease with ongoing signs and symptoms at the time of screening.
• Patients with CTCAE Grade 2 or higher peripheral neuropathy.
• History of significant cardiac disease: congestive cardiac failure \> NYHA class II, ongoing unstable angina, new-onset angina or myocardial infarction within the past 3 months

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

National University Hospital, Singapore

Singapore, 119228, Singapore

RECRUITING

Related Publications (2)

• Alam MM, Lal S, FitzGerald KE, Zhang L. A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. Clin Transl Med. 2016 Mar;5(1):3. doi: 10.1186/s40169-016-0082-9. Epub 2016 Jan 26.

  PMID: 26812134 BACKGROUND

• Vellinga TT, Borovski T, de Boer VC, Fatrai S, van Schelven S, Trumpi K, Verheem A, Snoeren N, Emmink BL, Koster J, Rinkes IH, Kranenburg O. SIRT1/PGC1alpha-Dependent Increase in Oxidative Phosphorylation Supports Chemotherapy Resistance of Colon Cancer. Clin Cancer Res. 2015 Jun 15;21(12):2870-9. doi: 10.1158/1078-0432.CCR-14-2290. Epub 2015 Mar 16.

  PMID: 25779952 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Andrea Wong, MBBS

CONTACT

(65) 6779 5555; andrea_la_wong@nuhs.edu.sg

Boon Cher Goh, MBBS

CONTACT

(65) 6779 5555; phcgbc@nuhs.edu.sg

Study Design

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

Model Details: Two parallel cohorts will be implemented: i. patients with tumors predicted to be dependent on oxidative phosphorylation metabolism or oncogene addicted tumors which have developed resistance to primary TKI therapy, or ii. patients with nasopharyngeal carcinoma

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: May 22, 2017
• Primary Completion: May 22, 2020
• Study Completion: November 30, 2020
• Last Updated: June 15, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)