Phase Ib/IIa Trial to Evaluate Oregovomab and Nivolumab in Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin (ORION-01)
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|ClinicalTrials.gov Identifier: NCT03100006|
Recruitment Status : Recruiting
First Posted : April 4, 2017
Last Update Posted : September 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Epithelial Ovarian Cancer||Drug: Nivolumab Drug: Oregovomab||Phase 1 Phase 2|
This study tests the hypothesis that the combination of Oregovomab and Nivolumab will improve intracellular Cancer Antigen (CA) 125 antigen processing and elicit a stronger systemic CA 125-specific T cell response; in a manner that is synergistic, safe, and clinically efficacious in patients with relapsed EOC.
This is an open-label, single-arm, phase Ib/IIa, single-center study with dose finding and dose expansion parts.
In the phase Ib part, clinically recommended doses as monotherapy for Oregovomab (IV 2 mg Q4W, dose level 1) and Nivolumab (IV 240 mg Q2W) will be the starting doses for their combined use.
A modified "3+3" dose finding design will be employed, with 2 lower dosages of Oregovomab (dose level -1 at 1 mg Q4W; level -2 at 0.5 mg Q4W) specified in case of excessive toxicity (defined as ≥ 2 dose limiting toxicities (DLTs) out of first 3 patients, or all 6 patients) encountered at dose level 1. Three patients will be initially enrolled into dose level 1. If 0 or 1 DLT is observed, another 3 patients will be enrolled into the same dose level; otherwise de-escalate and enroll 3 patients at dose level -1. If ≤ 1 DLT is observed among the 6 patients, dose level 1 will be the RDE/RP2D of Oregovomab to be combined with Nivolumab. Likewise, in the event of de-escalation, if 0 or 1 DLT is observed at a lower dose level, a further 3 patients will be enrolled for that level; if ≤ 1 DLT is observed out of the 6 patients, that dose level will be the RDE/RP2D.
A minimum of 6 and a maximum of 18 patients will be enrolled in the dose finding part.
Approximately 14 patients are to enroll in the dose expansion part wherein they will receive Oregovomab at RDE/RP2D, combined with Nivolumab. In total, 20 patients from the dose finding and dose expansion cohorts will be treated at RDE/RP2D, and be included in the phase IIa study population.
Patients will be followed up for survival and post-progression treatment(s) over a duration of up to 36 months from the time of treatment initiation (i.e., Week 0 until up to 36 months).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/IIa Clinical Trial to Evaluate the Safety and Activity of Oregovomab and Nivolumab as a Combinatorial Immunotherapy Strategy in Patients With Recurrent Epithelial Cancer of Ovarian, Tubal or Peritoneal Origin|
|Actual Study Start Date :||February 22, 2017|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
|Experimental: Nivolumab and Oregovomab||
240mg of IV Nivolumab is administered over 30 mins every 2 weeks
Other Name: Opdivo
IV Oregovomab is administered over 20 mins every 4 weeks at dose levels: 2mg, 1mg, or 0.5mg
Other Name: OvaRex
- Number of incidences and severity of Adverse Events (AE) and Serious AEs that are treatment-related, graded based on the CTCAE v4.03 [ Time Frame: 4 weeks from the start of treatment ]
- Overall response rate (ORR) as per Gynecological Cancer Intergroup (GCIG) criteria [ Time Frame: Time from date of start of treatment until best overall response of CR or PR, up to 3 years ]The proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR)
- Progression-free survival (PFS) as per GCIG criteria [ Time Frame: 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 ]
- ORR as per immune-related response criteria (irRC) [ Time Frame: Time from date of start of treatment until best overall response of CR or PR, up to 3 years ]The proportion of patients with best overall response of CR or PR
- Disease control rate (DCR) as per GCIG criteria and irRC [ Time Frame: Time from date of start of treatment until best overall response of CR, PR or SD, up to 3 years ]The proportion of patients with best overall response of CR, PR or Stable Disease (SD)
- ORR in EOC subtypes [ Time Frame: Time from date of start of treatment until best overall response of CR or PR, up to 3 years ]High Grade Serous, Clear Cell, Endometrioid, Mucinous, Mixed, Others and BRCA1/2 tumors
- Overall survival (OS) as per GCIG criteria [ Time Frame: Time from date of start of treatment to date of death due to any cause, up to 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03100006
|Contact: Jack Chan||+65 6436 email@example.com|
|Contact: Stella Chan||+65 6436 firstname.lastname@example.org|
|National Cancer Centre Singapore||Recruiting|
|Singapore, Singapore, 169610|
|Contact: Jack Chan, Dr 64368000 email@example.com|
|Principal Investigator:||Jack Chan||National Cancer Centre, Singapore|