A safety and efficacy study of the drug BGB-290 in combination with Temozolomide (TMZ) in patients with ovarian, breast, prostate, lung and stomach cancer.
- Conditions
- ocally Advanced or Metastatic Solid Tumors (ovarian cancer, triple negative breast cancer (TNBC), metastatic castration-resistant prostate cancer (mCRPC), small cell lung cancer (SCLC), and gastric cancer)
- Registration Number
- EUCTR2017-001553-14-GB
- Lead Sponsor
- BeiGene USA, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 250
All subjects:
1.Age =18 years old.
2.Confirmed malignancy at advanced or metastatic stage.
3.ECOG status = 1.
4.Adequate bone marrow function.
5.Adequate renal and hepatic function.
6. Agree to provide tumor archival tissue
Additional inclusion criteria 8 - 12 are specific to tumor types in dose expansion phase:
Ovarian cancer:
1.Previously received at least 1 line of platinum containing chemotherapy.
2.No progression or recurrent disease in 6 months from last platinum containing regimen.
Triple-Negative Breast Cancer
0 - 1 prior platinum-containing regimen (any treatment setting) and received = 3 prior regimens (advanced or metastatic setting).
Metastatic Castration-Resistant Prostate cancer
1.Documented progressive disease.
2.Chemotherapy-naïve or previously received =2 taxane-based regimens.
3.May be pre-or post-treatment with a novel androgen receptor targeted agent.
4.Completed in = 2 weeks radiation or treatment with anti-androgen agents.
Ovarian, breast and prostate cancer (BRCA+ or HRD+): If homologous recombinant deficiency (HRD) or BRCA status unknown, need pre-screening for eligibility.
Extensive Stage Small cell lung and Gastric/Gastroesophageal Junction
Cancer cancer: received = 2 prior lines of therapy.
HRD+ Solid Tumors. Multiple Indications (Expansion Cohort 6)
a. Patient has histologic or cytologic-confirmed advanced (metastatic and/or unresectable)
- nonsquamous non-small cell lung cancer (NSCLC)
- squamous NSCLC
- esophageal cancer
- squamous head and neck cancer
- soft-tissue sarcomas (undifferentiated pleomorphic sarcoma,leiomyosarcoma, malignant peripheral nerve sheath tumor, dedifferentiated liposarcoma, myxofibrosarcoma)
b. Patients must have tumors with homologous recombination deficiency (HRD+) as centrally determined by the Myriad myChoice® HRD Plus assay irrespective of any known molecular signature
c. Patients with nonsquamous NSCLC, squamous NSCLC, esophageal cancer and squamous head and neck cancer must have received at least 1 but not more than 3 prior lines of therapy
d. Patients with soft tissue sarcoma must have received at least 1 but no more than 3 prior lines of therapy. Treatment naïve patients may be allowed if, in the opinion of the investigator, available standard of care first line therapy is not appropriate
Other protocol-defined inclusion criteria may apply (see protocol for details).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
All subjects
1.Prior exposure to a PARP inhibitor.
2.Prior chemotherapy, biologic therapy, immunotherapy or investigational agents within 3 weeks prior to start of study treatment.
3.Refractory to platinum-based therapy.
4. Any unresolved toxicity of = Grade 2 from prior therapy.
5.Major surgery or significant injury = 4 weeks prior to start of study treatment.
6.History of other active malignancies within 2 years with exception of (i) adequately treated in situ carcinoma of the cervix, (ii) non-melanoma skin cancer, or (iii) localized adequately treated cancer with curative intent or malignancy diagnosed > 2 years ago with no evidence of disease and no treatment = 2 years prior to study treatment.
7.Untreated leptomeningeal or brain metastasis.
8.Active infection requiring systemic treatment.
9.Known human immunodeficiency virus (HIV) or active viral hepatitis.
10.Active, clinically significant cardiac disease or any Class 3 or 4 cardiac disease, ventricular arrhythmia or CVA = 6 months prior to start of treatment.
11.Active, clinically significant gastrointestinal disease.
12.Use of any medications or food known to be strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong inducers.
13.Pregnant or nursing females.
14. Have hereditary problems of galactose intolerance, the Lapp lactase
deficiency, or glucose-galactose malabsorption
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To determine the safety and tolerability of pamiparib (also known as<br>BGB-290)when given orally in combination with temozolomide (TMZ) (pulsed and continuous)<br>• To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ (pulsed and continuous)<br>• To select the recommended Phase 2 dose (RP2D) and schedule of BGB-290 in combination with TMZ<br>• To determine the preliminary antitumor activity of pamiparib in<br>combination with TMZ;Secondary Objective: • To characterize the pharmacokinetics (PK) of BGB-290 and TMZ;Primary end point(s): Expansion: Incidence, nature, and severity of AEs, graded according to the NCI CTCAE v. 4.03<br>Objective response rate (ORR), as assessed using RECIST v1.1;Timepoint(s) of evaluation of this end point: during weekly visits; for AE collection: during weekly visits for the first 5 cycles, every 28 days after cycle 5, EOT, safety follow-up visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1) Pharmacokinetic (PK) parameters (Cmax) of pamiparib and TMZ<br>2) Pharmacokinetic (PK) parameters (Tmax) of pamiparib and TMZ<br>3) Objective response rate (ORR) as assessed using RECIST v 1.1<br>4) Duration of response (DOR)<br>5) Disease control rate (DCR)<br>6) Progression free survival (PFS)<br>7) Overall survival (OS);Timepoint(s) of evaluation of this end point: 1,2: Cycle 1 Day 1/7/15<br>3, 4, 5, 6: Within 4 weeks prior to Day 1; every 8 weeks; EOT; every 8 weeks during Efficacy Follow-up<br>7: Every 3 months post EOT<br>