Phase 2 Study of Combination of Nivolumab and Ipilimumab in (1) Neoadjuvant Setting in Previously Untreated Breast Cancer Patients, (2) Platinum-Resistant/Refractory Advanced Ovarian Cancer Patients; and (3) Advanced Gastric Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Breast Cancer Female
- Sponsor
- ExcellaBio LLC
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Clinical Response
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
Safety and tolerability of combination of Nivolumab and Ipilimumab will be studied in patients with 3 different types of cancers in 3 parts of the study, as shown below:
Part 1 - Neoadjuvant Therapy of Breast Cancer;
Part 2 - Therapy of Ovarian Cancer; and
Part 3 - Therapy of Gastric Cancer.
Detailed Description
Open-Label, Non-Randomization and Safety Run-In: Part 1 of the study is a Phase 2 clinical trial in 20 newly diagnosed patients who have Stage II-III breast cancer, with the primary cancer in place. Parts 2 and 3 of the Study are Phase 2 clinical trials in 20 platinum resistant refractory ovarian cancer (PRROC) and gastric cancer patients, respectively. Also in all Parts 1, 2 and 3 of the study, there will be a safety run-in involving 3-6 patients. Specifically, the enrollment of patients in each of the 3 parts of the study will begin with 3 patients. If no dose-limiting toxicities (DLTs, defined as toxicity ≥Grade 3) are observed in the first 3 patients during the first cycle, enrollment can continue for the remaining 17 patients. If 1 of the first 3 patients experiences a DLT, the enrollment will be expanded to a total of 6 subjects. If no more than 1 of 6 subjects experiences a DLT, enrollment can continue for the remaining 14 patients. If 2 or more of the first 2-6 subjects experience a DLT, enrollment may be paused. The study data will be reviewed to determine whether alternate dose levels or treatment schedules should be evaluated.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must meet all inclusion criteria before enrollment:
- •For Part 1 of the study (i.e., neoadjuvant therapy of breast cancer):
- •A. Stage II-III disease, with primary cancer in place, invasive breast cancer confirmed by core needle biopsy (CNB) or incisional biopsy (excisional biopsy is not allowed):
- •fluorescence in situ hybridization (FISH) negative. (Note: Patients who are HER2Neu+3 or HER2Neu+ by FISH are excluded, as there is FDA approved therapy with known clinical benefit in the neoadjuvant setting.)
- •the disease is previously untreated, operable, and intend to undergo surgery (e.g., a mastectomy or lumpectomy) after completion of neoadjuvant therapy
- •the disease must be radiographically measurable in the breast. (radiographically measurable disease is defined as longest diameter ≥1.0 cm)
- •the disease cannot be axillary disease only (i.e., no identifiable tumor in the breast that is ≥1.0 cm on physical exam or radiographic study)
- •the disease can be multi-centric or bilateral disease, provided the target lesion meets the above eligibility criteria
- •breast cancer patients with lobular and ductal histology will be included. (Note: In patients with clinically positive axillae, histologic confirmation by biopsy or fine-needle aspiration may be performed.) B. Females ≥18 years of age. C. Females of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use effective contraceptive methods (such as abstinence, intrauterine device \[IUD\], or double barrier device, and hormonal contraception such as birth control pills cannot be used) during the study and for at least 3 months following completion of the study, and must have a negative serum or urine pregnancy test within 2 weeks prior to treatment initiation.
- •D. Mentally competent, able to understand and willingness to sign the informed consent form.
Exclusion Criteria
- •Patients with any of the following characteristics will be excluded:
- •For Parts 1, 2 and 3 of the study (i.e., neoadjuvant therapy of breast cancer and therapies of ovarian cancer and gastric cancer, respectively):
- •A. Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 6 months, uncontrolled or symptomatic cardiac arrhythmia, or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity
- •B. Arterial thrombotic event, stroke, or transient ischemia attack within the past 12 months
- •C. Uncontrolled hypertension (systolic blood pressure \>160 mm Hg or diastolic blood pressure \>90 mm Hg), or peripheral vascular disease ≥grade 2
- •D. Active central nervous system (CNS), epidural tumor or metastasis, or brain metastasis.
- •E. Any active uncontrolled bleeding, or a bleeding diathesis.
- •F. Evidence of active infection during screening, and any acute therapy needs to be completed within 7 days prior to enrollment.
- •G. Patients with known Human Immunodeficiency Virus (HIV) infection, known active viral hepatitis A, B and C, or known history of tuberculosis, even if treated and in remission. (Noninfectious liver disease is allowed, i.e., NASH or cirrhosis classes A and B, but not C.)
- •H. Serious or non-healing wound, skin ulcer, or non-healing bone fracture
Outcomes
Primary Outcomes
Clinical Response
Time Frame: 2 years
Part 1 of the Study in Breast Cancer Patients - Clinical response of the investigational neoadjuvant therapy based on pathological Complete Response (pCR) rate; Part 2 of the Study in Ovarian Cancer Patients - Clinical response of the investigational therapy based on Best Objective Response (BOR) and overall response rate (ORR); and Part 3 of the Study in Gastric Cancer Patients - Clinical response of the investigational therapy based on Best Objective Response (BOR) and overall response rate (ORR)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 1 year
For all 3 parts of the study - Adverse changes in blood work and urinalysis and appearance of adverse events during and after treatment in patients will be assessed
Secondary Outcomes
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - PFS(2 years)
- Part 2 of the Study (Therapy of Ovarian Cancer) and Part 3 of the Study (Therapy of Gastric Cancer) - DOR(2 years)
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - BCT(2 years)
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Possible predictive biomarkers(2 years)
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Possible transition of Th2 to Th1 in the tumor(2 years)
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Status of PD-L1, PDL-2, and PD-1 in tumor tissues before vs. after investigational neoadjuvant therapy(2 years)
- Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - BOR and ORR(2 years)
- Part 2 of the Study (Therapy of Ovarian Cancer) and Part 3 of the Study (Therapy of Gastric Cancer) - OS(2 years)
- Part 2 of the Study (Therapy of Ovarian Cancer) and Part 3 of the Study (Therapy of Gastric Cancer) - Recurrence rate(2 years)