Atezolizumab With Neoadjuvant Chemotherapy for Patients With Newly-Diagnosed Advanced-Stage Ovarian Cancer

NCT03394885 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00079313
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

The main purpose of this study is to validate a safe dose of atezolizumab with dose-dense paclitaxel and carboplatin when utilized with neoadjuvant chemotherapy and interval cytoreductive surgery followed by maintenance atezolizumab in women with advanced ovarian cancer.

Conditions

Ovarian Cancer; Ovarian Neoplasms

Outcome Measures

Primary Outcomes (4)

• Safety: Incidence of Post Chemotherapy Surgical Debulking

  The number of subjects able to undergo interval cytoreductive surgery will be utilized as a measure of safety regarding the initial dosing of atezolizumab.

  9 weeks

• Safety: Incidence of Treatment Emergent Adverse Events

  The number of adverse events experienced while receiving study drugs will be utilized to assess safety of atezolizumab.

  18 months

• Safety: Dose Intensity

  Percentage of planned doses of atezolizumab received at each cycle (21 day period) will be utilized as a measure of safety and tolerability for each subject.

  Cycles 1-6,18 months total

• Safety: Incidence of Dose Modifications

  The number of dose modifications for atezolizumab at each cycle (21 day period) will be utilized as a measure of safety and tolerability for each subject. Dose modifications are defined as doses delayed, doses discontinued, or doses held.

  Cycles 1-6,18 months total

Secondary Outcomes (4)

• Number of Participants With a Complete or Partial Response as Measured by RECIST (Response Evaluation Criteria in Solid Tumors)

  18 months

• Number of Participants With Pathologic Complete Remission

  9 weeks

• Progression Free Survival Rate

  18 months

• Overall Survival Rate

  18 months

Other Outcomes (5)

• Translational: PD-L1 Expression

  18 months

• Translational: Tumor Infiltrating Lymphocytes

  18 months

• Translational: Immune Checkpoint Receptors

  18 months

Study Arms (1)

Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)

EXPERIMENTAL

1. Atezolizumab administered over 90 (± 15) minutes (for the first infusion, shortening to 60 (± 15) minutes and 30 ± 15) minutes for subsequent infusions as described below) followed by 2. Paclitaxel 70-80mg/m2 IV administered over approximately one hour followed by 3. Carboplatin IV administered over 15-30 minutes to achieve an initial target AUC of 5-6 mg/mL/Min (Calvert formula dosing). 4. (Optional, Physician choice) Bevacizumab IV maintenance administered starting at cycle 5 of chemotherapy over 30-90 minutes. For those who receive bevacizumab, it will be given for a total duration of 16 cycles

Drug: Atezolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

1200mg IV q3weeks

Also known as: Tecentriq

Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)

Carboplatin DRUG

5-6mg/ML IV q3 weeks

Also known as: Paraplatin

Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)

Paclitaxel DRUG

70-80 mg/m2 IV q1 week

Also known as: Taxol

Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)

Bevacizumab DRUG

15 mg/kg IV q3 weeks

Also known as: Avastin

Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form (ICF)
• Ability and willingness to comply with the requirements of the study protocol
• Age ≥ 18 years
• No prior treatment for primary advanced (stage III or IV) epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
• Confirmation of diagnosis (by surgical excisional/incisional biopsy or imaging-guided core biopsy), and patients for whom the plan of management will include NACT followed by ICS. The decision to proceed with NACT will be at the treating physician's discretion and include patients with advanced stage disease considered at low likelihood for optimal cytoreduction with primary debulking surgery.
• All patients must have measurable disease per RECIST v1.1
• Patients must meet the following criteria prior to initiation of study treatment:
• Histology consistent with high-grade epithelial ovarian cancer (excluding mucinous carcinoma, clear cell carcinoma, and carcinosarcoma)
• An adequate pre-treatment tumor biopsy is required to confirm histologic diagnosis. Acceptable options include laparoscopic biopsy or image-guided core needle biopsy (minimum of two cores). Fine needle aspiration (FNA) biopsy or cytology from ascites is not adequate.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 (see Appendix 6)
• Peripheral neuropathy less than or equal to CTCAE Grade 1
• For female patients of childbearing potential, agreement (by patient) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \[\< 1% per year\] when used consistently and correctly) and to continue its use at least until ICS or if ICS is not performed then 90 days post last dose of atezolizumab

You may not qualify if:

• Mucinous, low-grade histology, clear cell carcinoma, or carcinosarcoma
• Prior systemic chemotherapy for epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. (Exceptions include basal cell or squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.)
• AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
• Bisphosphonate therapy for symptomatic hypercalcemia
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
• Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
• Pregnancy, lactation, or breastfeeding
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Inability to comply with study and follow-up procedures
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
• Active tuberculosis

Sponsors & Collaborators

• Duke University: lead
• Johns Hopkins University: collaborator
• Genentech, Inc.: collaborator

Study Sites (3)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

atezolizumab; Carboplatin; Paclitaxel; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Angeles Alvarez Secord
• Organization: Duke Cancer Center

angeles.secord@duke.edu

919-684-3765

Study Officials

• Angeles A Secord, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2017
• First Posted: January 9, 2018
• Study Start: June 19, 2018
• Primary Completion: July 20, 2020
• Study Completion: July 20, 2020
• Last Updated: August 12, 2021
• Results First Posted: August 10, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)