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

NCT ID: NCT03158324

Last Updated: 2017-06-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-22
• Study Completion Date: 2020-11-30

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.

Detailed Description

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. Patients on the proposed study will be treated with the RPII dose of OPB-111077 (600mg on a 4 days-on, 3 days-off per week schedule). They will be enrolled in two parallel cohorts: 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

Each cohort will contain 11-26 patients, over a period of 12-36 months. Subjects will receive OPB-111077 in 28-day cycles till disease progression or intolerable toxicity. Mandatory tumour biopsies will be performed at baseline and on cycle 1 day 15 (where feasible and accessible). Circulating biomarker blood sampling will be performed on days 1, 11 and 15 of cycle 1, and upon completion of OPB-111077 dosing. Pharmacokinetics blood sampling will be performed on days 11 and 15 of cycle 1. Safety assessments will be performed on cycle 1 day 1, cycle 1 day 8, cycle 1 day 15, bi-weekly till week 8, then monthly thereafter and response assessments will be performed every 8 weeks. Metabolic response assessment by PET/CT will be performed after 2 cycles of treatment, while radiologic response assessment will be performed after every 2 cycles of OPB-111077 from cycle 4 onwards.

Conditions

NPC; Refractory Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Advanced refractory solid tumors

Patients with advanced refractory solid tumors will be enrolled.

Group Type: EXPERIMENTAL

OPB-111077

Intervention Type: 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

Interventions

OPB-111077

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed, locally recurrent or metastatic solid tumors, who have failed standard treatment

2. Subjects with NPC will be eligible as long as they have received prior platinum therapy

3. 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

4. All subjects must have at least one tumour lesion (primary or metastatic) that is suitable for free-hand or image-guided biopsy at baseline.

5. Age ≥ 21 years, Eastern Cooperative Oncology Group (ECOG) performance status < 1

6. Adequate bone marrow, liver and renal function

7. Baseline serum lactate ¬<3mmol/l

8. Capable of swallowing tablets

9. 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.

10. Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.

Exclusion Criteria

1. Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 3 weeks of starting investigational medicinal product (IMP).

2. 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

3. Pregnancy or breastfeeding.

4. 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.

5. Known or suspected allergy to the investigational agent or any agent given in association with this study.

6. 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.

7. Interstitial lung disease with ongoing signs and symptoms at the time of screening.

8. Patients with CTCAE Grade 2 or higher peripheral neuropathy.

9. 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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National University Hospital, Singapore

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Andrea Wong, MBBS

Role: CONTACT

andrea_la_wong@nuhs.edu.sg

(65) 6779 5555

Boon Cher Goh, MBBS

Role: CONTACT

phcgbc@nuhs.edu.sg

(65) 6779 5555

Facility Contacts

Andrea Wong, MBBS

Role: primary

Andrea_LA_Wong@nuhs.edu.sg

+65 6772 4621

References

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.

Reference Type: BACKGROUND

PMID: 26812134 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25779952 (View on PubMed)

Other Identifiers

2016/01181

Identifier Type: -

Identifier Source: org_study_id