Phase Ib/IIa Trial to Evaluate Oregovomab and Nivolumab in Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin

NCT03100006 | Terminated Phase 1

• 1 other identifier: NCC OV-02
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the safety and tolerability, identify a recommended dose for expansion (RDE) / recommended phase II dose (RP2D), pharmacodynamics, and antitumor activity of Oregovomab vaccination in combination with Nivolumab as a novel combinatorial immunotherapeutic strategy in in female patients with recurrent epithelial ovarian cancer (EOC) who progressed after two or more prior lines of cytotoxic chemotherapy.

Conditions

Epithelial Ovarian Cancer

Outcome Measures

Primary Outcomes (3)

• Number of incidences and severity of Adverse Events (AE) and Serious AEs that are treatment-related, graded based on the CTCAE v4.03

  4 weeks from the start of treatment

• Overall response rate (ORR) as per Gynecological Cancer Intergroup (GCIG) criteria

  The proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR)

  Time from date of start of treatment until best overall response of CR or PR, up to 3 years

• Progression-free survival (PFS) as per GCIG criteria

  Time from date of start of treatment to the date of the first documented progression or death due to any cause, up to 3 years

Secondary Outcomes (4)

• ORR as per immune-related response criteria (irRC)

  Time from date of start of treatment until best overall response of CR or PR, up to 3 years

• Disease control rate (DCR) as per GCIG criteria and irRC

  Time from date of start of treatment until best overall response of CR, PR or SD, up to 3 years

• ORR in EOC subtypes

  Time from date of start of treatment until best overall response of CR or PR, up to 3 years

• Overall survival (OS) as per GCIG criteria

  Time from date of start of treatment to date of death due to any cause, up to 3 years

Study Arms (1)

Nivolumab and Oregovomab

EXPERIMENTAL

Drug: Nivolumab; Drug: Oregovomab

Interventions

Nivolumab DRUG

240mg of IV Nivolumab is administered over 30 mins every 2 weeks

Also known as: Opdivo

Nivolumab and Oregovomab

Oregovomab DRUG

IV Oregovomab is administered over 20 mins every 4 weeks at dose levels: 2mg, 1mg, or 0.5mg

Also known as: OvaRex

Nivolumab and Oregovomab

Eligibility Criteria

• Age: 21 Years - 99 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Written Informed Consent
• Able to understand and voluntarily sign the Informed Consent Form (ICF). Written informed consent must be obtained before any study specific procedures that are not part of standard of care.
• Willing and able to comply with scheduled visits, treatment schedule, laboratory test, and other protocol requirements
• Age and Target Population
• Age ≥ 21 years old
• Histologically and/or cytologically confirmed diagnosis of epithelial ovarian carcinoma (serous, clear cell, endometrioid, mucinous, mixed, and others), fallopian tube and primary peritoneal carcinoma
• Serum CA 125 level at enrollment must be at least twice the upper limit of normal (ULN) using local laboratory ranges
• Objective evidence of disease recurrence following initial curative-intent treatment, and of progression after at least 2 prior lines of cytotoxic chemotherapy (including platinum and taxane) for advanced stage disease. Patients may have received prior treatment with Bevacizumab.
• Presence of:
• (a) measurable disease as defined by RECIST v1.1 AND a pre-treatment serum CA 125 level ≥ 2 x ULN on 1 occasion, OR (b) non-measurable but evaluable disease such as ascites and pleural effusions attributable to disease or radiologic abnormalities that do not meet RECIST v1.1 criteria AND a pre-treatment serum CA 125 level ≥ 2 x ULN on 2 occasions at least 1 week apart, OR (c) non-evaluable, non-measurable disease as defined by RECIST v1.1 AND pre-treatment CA 125 level ≥ 2 x ULN on 2 occasions at least 1 week apart
• Estimated life expectancy greater than 3 months
• Performance status Eastern Cooperative Oncology Group (ECOG) 0 or 1
• Adequate hematologic and end organ function, defined by the following local laboratory results obtained within 14 days before study entry:
• Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
• White Blood Cells (WBC) count ≥ 2.0 × 109/L

You may not qualify if:

• Non-epithelial ovarian tumors, including malignant mixed Müllerian tumors (carcinosarcoma), or ovarian tumors with low malignant potential (i.e., borderline tumors).
• Active symptomatic central nervous system (CNS) metastases. Patients with previous CNS metastases are eligible provided that they underwent CNS irradiation, are asymptomatic, do not require treatment with radiation therapy or anticonvulsants, and have stable disease at the screening tumor assessment. In addition, these patients must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisolone (or equivalent).
• Spinal cord compression not definitively treated with surgery and/or radiation. Patients with previously diagnosed and treated spinal cord compression are eligible provided that they have stable disease at the screening tumor assessment. In addition, these patients must have been either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisolone (or equivalent).
• Leptomeningeal carcinomatosis
• Uncontrolled pleural effusion(s), pericardial effusion, or ascites requiring recurrent drainage procedures
• o Patients with functioning pleural and/or peritoneal drainage catheters/devices in situ at time of study entry may be eligible.
• Previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years before study entry AND no additional therapy is required, or anticipated to be required, during the study period.
• Pregnant or lactating women
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months before study entry, unstable arrhythmias/heart block, or unstable angina
• o Patients with a known left ventricular ejection fraction (LVEF) \< 40% or pre-existing poorly controlled hypertension (systolic blood pressure \> 160 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management) will be excluded.
• Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
• Patients with stable cardiac arrhythmia requiring stable dose(s) of anti-arrhythmic therapy may be eligible.
• Severe infections within 4 weeks before study entry including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant traumatic injury, or major surgical procedure within 4 weeks before study entry, or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

Nivolumab; oregovomab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; 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)

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

Study Officials

• Jack Chan

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

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: March 21, 2017
• First Posted: April 4, 2017
• Study Start: February 22, 2017
• Primary Completion: June 7, 2019
• Study Completion: April 17, 2020
• Last Updated: June 13, 2022

Record last verified: 2022-06

Locations

SG (1)