Combination of Nivolumab and Ipilimumab in Breast, Ovarian and Gastric Cancer Patients

NCT03342417 | Terminated Phase 2 FDA Drug

• 1 other identifier: CA209-929
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer Female; Ovarian Cancer; Gastric Cancer

Keywords

breast cancer; ovarian cancer; gastric cancer

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  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

  1 year

• Clinical Response

  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)

  2 years

Secondary Outcomes (9)

• 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) - 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) - Possible transition of Th2 to Th1 in the tumor

  2 years

• Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - BOR and ORR

  2 years

Other Outcomes (23)

• Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Tumor Genomics and Biomarkers

  2 years

• Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Circulating DNA

  2 years

• Part 1 of the Study (Neoadjuvant Therapy of Breast Cancer) - Immune Cell Activation Markers

  2 years

Study Arms (3)

Neoadjuvant Breast Cancer

EXPERIMENTAL

Newly diagnosed patients who have Stage II-III breast cancer, with the primary cancer in place. These patients have not received prior therapy for their breast cancer and intend to undergo surgery after completion of investigational neoadjuvant therapy. Each patient will be treated with two 6-week treatment cycles of Nivolumab 240 mg administered by intravenous (IV) infusion over 30 minutes and Ipilimumab 1 mg/kg administered by IV infusion over 30 minutes. Nivolumab is given every two weeks (q2w) whereas Ipilimumab is given every 6 weeks (q6w), both starting on Day 1. Accordingly, Nivolumab and Ipilimumab are given on the same day on Days 1 and 43. On these days, Ipilimumab is to be given immediately after Nivolumab.

Biological: Nivolumab; Biological: Ipilimumab

Platinum-resistant ovarian cancer

EXPERIMENTAL

Platinum-resistant/refractory ovarian cancer (PRROC) patients. Each patient will be treated with four 6-week treatment cycles of Nivolumab 240 mg administered by IV infusion over 30 minutes and Ipilimumab 1 mg/kg administered by IV infusion over 30 minutes. Nivolumab is given q2w whereas Ipilimumab is given q6w, both starting on Day 1. Accordingly, Nivolumab and Ipilimumab are given on the same day on Days 1, 43, 85 and 127. On these days, Ipilimumab is to be given immediately after Nivolumab.

Biological: Nivolumab; Biological: Ipilimumab

Advanced gastric cancer patients

EXPERIMENTAL

Advanced gastric cancer patients who are recurrent/refractory to a prior therapy not involving herceptin. Each patient will be treated with four 6-week treatment cycles of Nivolumab and Ipilimumab . Nivolumab is given q2w whereas Ipilimumab is given q6w, both starting on Day 1. Accordingly, Nivolumab and Ipilimumab are given on the same day on Days 1, 43, 85 and 127. On these days, Ipilimumab is to be given immediately after Nivolumab.

Biological: Nivolumab; Biological: Ipilimumab

Interventions

Nivolumab BIOLOGICAL

Nivolumab 240 mg administered by IV infusion over 30 minutes

Also known as: OPDIVO

Advanced gastric cancer patients; Neoadjuvant Breast Cancer; Platinum-resistant ovarian cancer

Ipilimumab BIOLOGICAL

Ipilimumab 1 mg/kg administered by IV infusion over 30 minutes.

Also known as: YERVOY

Advanced gastric cancer patients; Neoadjuvant Breast Cancer; Platinum-resistant ovarian cancer

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Part 1. Neoadjuvant Breast (Females ≥18 years of age) Part 2. Platinum-resistant refractory ovarian (Females ≥18 years of age.) Part 3. Advanced Gastric Cancer (Male or female ≥18 years of age)
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• E. At least 4 weeks must have elapsed from any prior major surgery. The following procedures are not considered major surgical procedure:
• Obtaining the required research needle biopsies
• Placement of a radiopaque clip to localize a tumor or tumors for subsequent surgical resection
• Placement of a port for central venous access
• Fine needle aspiration of a prominent or suspicious axillary lymph node
• Needle biopsy of a clinically or radiographically detected lesion to rule out metastatic disease

You may not qualify if:

• 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
• I. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.
• J. A history of colitis.
• K. Albumin \<2.5 g/dL or \<25 g/L.
• L. Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
• M. Unwilling or unable to follow protocol requirements.
• N. Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication within the past 3 weeks prior to participating in the study.

Sponsors & Collaborators

• ExcellaBio LLC: lead

Study Sites (1)

Hoffman Oncology

The Bronx, New York, 10469, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Stomach Neoplasms; Breast Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Anthony Hoffman, MD

  ExcellaBio LLC

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open-Label, Non-Randomization Phase 2 clinical trial with Safety Run-In (3 parts): Part 1 in 20 newly diagnosed patients who have Stage II-III breast cancer, with the primary cancer in place. These patients have not received prior therapy and intend to undergo surgery after completion of investigational neoadjuvant therapy. Parts 2 and 3 in 20 PRROC and gastric cancer patients, respectively. Enrollment of patients in each of the 3 parts will begin with 3 patients. If no dose-limiting toxicities (DLTs, defined as toxicity ≥Grade 3) are observed 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 and the study data will be reviewed.

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: November 17, 2017
• Study Start: February 14, 2018
• Primary Completion: May 29, 2019
• Study Completion: May 29, 2019
• Last Updated: November 9, 2021

Record last verified: 2021-11

Locations

US (1)