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Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy (Parpvax)

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ClinicalTrials.gov Identifier: NCT03404960
Recruitment Status : Active, not recruiting
First Posted : January 19, 2018
Results First Posted : July 3, 2023
Last Update Posted : March 26, 2024
Sponsor:
Collaborators:
Bristol-Myers Squibb
GlaxoSmithKline
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Adenocarcinoma
Interventions Drug: Niraparib + Nivolumab
Drug: Niraparib + Ipilimumab
Enrollment 104
Recruitment Details  
Pre-assignment Details 104 subjects enrolled. 11 failed eligibility criteria. 2 withdrew consent. 91 randomly assigned and included in the safety analysis.
Arm/Group Title Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Hide Arm/Group Description

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.
Period Title: Overall Study
Started 46 45
Completed 44 40
Not Completed 2 5
Reason Not Completed
Adverse Event             0             2
Rapidly declined before 1st follow-up scan             0             2
Bowel obstruction             0             1
Incorrect pathological diagnosis on internal review             2             0
Arm/Group Title Arm A Arm B Total
Hide Arm/Group Description

Niraparib + Nivolumab

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Ipilimumab

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.

 Total of all reporting groups
Overall Number of Baseline Participants 44 40 84
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 40 participants 84 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
18
  40.9%
23
  57.5%
41
  48.8%
>=65 years
26
  59.1%
17
  42.5%
43
  51.2%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 44 participants 40 participants 84 participants
68
(46 to 84)
64
(48 to 81)
66
(46 to 84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 40 participants 84 participants
Female
15
  34.1%
20
  50.0%
35
  41.7%
Male
29
  65.9%
20
  50.0%
49
  58.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 40 participants 84 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   4.5%
0
   0.0%
2
   2.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   6.8%
3
   7.5%
6
   7.1%
White
38
  86.4%
37
  92.5%
75
  89.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.3%
0
   0.0%
1
   1.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 44 participants 40 participants 84 participants
44 40 84
1.Primary Outcome
Title Rate of Progression-free Survival at 6 Months (PFS6)
Hide Description

The PFS6 rate will be estimated using the Kaplan-Meier method, and the 95% confidence interval will be estimated from the Kaplan-Meier curve. The null hypothesis is that the PFS6 rate in this population of subjects is 44%.

Progressive disease is defined as at least a 20% increase in the sum of all the longest diameter (LD) of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions is also considered progression.

Target lesions assessed according to RECIST v1.1.
Time Frame 6 months after initiation of study therapy
Hide Outcome Measure Data
Hide Analysis Population Description
The efficacy population will consist of all patients who received at least one dose of study treatment and had a least one post-treatment assessment of response by RECIST v.1.1.
Arm/Group Title Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Hide Arm/Group Description:

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.
Overall Number of Participants Analyzed 44 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants with PFS
20.6
(8.3 to 32.9)
59.6
(44.3 to 74.9)
2.Secondary Outcome
Title Safety and Tolerability of This Combination as Determined by CTCAE v5.0.
Hide Description The incidence of adverse events (AEs), clinical laboratory abnormalities and dose modifications.
Time Frame From the initiation of any study intervention through 100 days (nivolumab patients) or 90 days (all patients) after patient End of Treatment Visit
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Proportion of Tumors With Homologous Recombination Deficits (HRD), in Patients With Stability or Response to Platinum Therapy
Hide Description Identification of HRDs and allele specific LOH via whole exome sequencing
Time Frame Cycle 1 Day 1 through completion of study treatment (maximum 42 months)
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Correlation of HRDs With Response to Treatment With Niraparib Plus Immune Checkpoint Blockade
Hide Description Identification of HRDs and allele specific LOH via whole exome sequencing
Time Frame Cycle 1 Day 1 through completion of study treatment (maximum 42 months)
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Immune Activation Prior to Treatment
Hide Description Assessed using immune biomarkers, and RNAseq of PBMC
Time Frame Prior to initiation of study therapy (maximum 36 months)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Immune Activation During Treatment
Hide Description Assessed using immune biomarkers, and RNAseq of PBMC
Time Frame Following receipt of study therapy and through study completion (maximum 42 months)
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Overall Response Rate
Hide Description Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
Time Frame From first restaging assessment through completion of study treatment (maximum 42 months)
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Duration of Response (DOR)
Hide Description Measured by CT scans and other studies (MRI, X-ray, PET, and ultrasound)
Time Frame From first restaging assessment until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Overall Survival (OS)
Hide Description start of treatment to death due to any cause or last patient contact alive
Time Frame Cycle 1 Day 1 until death, loss to follow-up, withdrawal of consent or until 5 years have passed, whichever occurs first
Outcome Measure Data Not Reported
Time Frame 6 months after initiation of study therapy
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Hide Arm/Group Description

Niraparib + Nivolumab: Niraparib 200mg PO daily on days 1-28 of each 28-day cycle.

Nivolumab 480mg IV day 1 of each cycle.

Niraparib + Ipilimumab: Niraparib 200mg PO daily on days 1-21 of each 21-day cycle.

Ipilimumab 3mg/kg IV day 1 of each cycle, for the first 4 cycles only.
All-Cause Mortality
Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Affected / at Risk (%) Affected / at Risk (%)
Total   7/46 (15.22%)      5/45 (11.11%)    
Hide Serious Adverse Events
Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/46 (43.48%)      15/45 (33.33%)    
Cardiac disorders     
Myocardial infarction † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain † 1  2/46 (4.35%)  2 0/45 (0.00%)  0
Ascites † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Colitis † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Duodenal ulcer † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Gastric hemorrhage † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Obstruction gastric † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Pancreatitis † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Small intestinal obstruction † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
General disorders     
Fever † 1  1/46 (2.17%)  1 1/45 (2.22%)  1
Hepatobiliary disorders     
Other: Acute cholangitis † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Infections and infestations     
Biliary tract infection † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Sepsis † 1  1/46 (2.17%)  1 1/45 (2.22%)  1
Investigations     
Blood bilirubin increased † 1  2/46 (4.35%)  2 0/45 (0.00%)  0
Platelet count decreased † 1  1/46 (2.17%)  1 2/45 (4.44%)  2
Metabolism and nutrition disorders     
Hyperkalemia † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Hyponatremia † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Nervous system disorders     
Dysarthria † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Stroke † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Psychiatric disorders     
Confusion † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Suicide attempt † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Other: Passing gallbladder obstruction † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pneumonitis † 1  2/46 (4.35%)  2 1/45 (2.22%)  1
Pulmonary edema † 1  0/46 (0.00%)  0 1/45 (2.22%)  1
Skin and subcutaneous tissue disorders     
Rash maculo-papular † 1  0/46 (0.00%)  0 2/45 (4.44%)  2
Vascular disorders     
Hypertension † 1  1/46 (2.17%)  1 0/45 (0.00%)  0
1
Term from vocabulary, CTCAE 5.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Niraparib + Nivolumab (Arm A) Niraparib + Ipilimumab (Arm B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   46/46 (100.00%)      44/45 (97.78%)    
Blood and lymphatic system disorders     
Anemia † 1  10/46 (21.74%)  30 20/45 (44.44%)  41
Cardiac disorders     
Palpitations † 1  0/46 (0.00%)  0 3/45 (6.67%)  3
Gastrointestinal disorders     
Abdominal distension † 1  3/46 (6.52%)  4 1/45 (2.22%)  1
Abdominal pain † 1  18/46 (39.13%)  26 12/45 (26.67%)  15
Constipation † 1  7/46 (15.22%)  7 7/45 (15.56%)  7
Diarrhea † 1  6/46 (13.04%)  9 12/45 (26.67%)  17
Dry mouth † 1  1/46 (2.17%)  1 3/45 (6.67%)  6
Gastroesophageal reflux disease † 1  0/46 (0.00%)  0 3/45 (6.67%)  3
Mucositis oral † 1  2/46 (4.35%)  2 3/45 (6.67%)  3
Nausea † 1  16/46 (34.78%)  20 20/45 (44.44%)  25
Vomiting † 1  7/46 (15.22%)  12 8/45 (17.78%)  12
General disorders     
Chills † 1  3/46 (6.52%)  4 4/45 (8.89%)  4
Fatigue † 1  13/46 (28.26%)  18 26/45 (57.78%)  40
Fever † 1  8/46 (17.39%)  10 10/45 (22.22%)  11
Pain † 1  9/46 (19.57%)  13 4/45 (8.89%)  4
Infections and infestations     
Urinary tract infection † 1  3/46 (6.52%)  4 1/45 (2.22%)  2
Investigations     
Alanine aminotransferase increased † 1  10/46 (21.74%)  25 20/45 (44.44%)  30
Alkaline phosphatase increased † 1  14/46 (30.43%)  27 17/45 (37.78%)  20
Aspartate aminotransferase increased † 1  12/46 (26.09%)  33 22/45 (48.89%)  37
Blood bilirubin increased † 1  7/46 (15.22%)  13 5/45 (11.11%)  6
Creatinine increased † 1  5/46 (10.87%)  8 9/45 (20.00%)  13
Neutrophil count decreased † 1  8/46 (17.39%)  14 7/45 (15.56%)  13
Platelet count decreased † 1  18/46 (39.13%)  41 21/45 (46.67%)  43
Thyroid stimulating hormone increased † 1  1/46 (2.17%)  1 3/45 (6.67%)  4
Weight loss † 1  5/46 (10.87%)  5 6/45 (13.33%)  6
White blood cell decreased † 1  3/46 (6.52%)  8 4/45 (8.89%)  11
Metabolism and nutrition disorders     
Anorexia † 1  5/46 (10.87%)  6 6/45 (13.33%)  8
Hyperkalemia † 1  0/46 (0.00%)  0 4/45 (8.89%)  5
Hypocalcemia † 1  4/46 (8.70%)  6 5/45 (11.11%)  10
Hypokalemia † 1  4/46 (8.70%)  6 5/45 (11.11%)  7
Hypomagnesemia † 1  8/46 (17.39%)  8 11/45 (24.44%)  16
Hyponatremia † 1  10/46 (21.74%)  17 11/45 (24.44%)  17
Hypophosphatemia † 1  3/46 (6.52%)  5 1/45 (2.22%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  6/46 (13.04%)  11 7/45 (15.56%)  9
Back pain † 1  7/46 (15.22%)  7 8/45 (17.78%)  10
Nervous system disorders     
Dizziness † 1  3/46 (6.52%)  3 2/45 (4.44%)  2
Dysgeusia † 1  3/46 (6.52%)  3 1/45 (2.22%)  1
Headache † 1  7/46 (15.22%)  10 6/45 (13.33%)  8
Psychiatric disorders     
Insomnia † 1  7/46 (15.22%)  7 2/45 (4.44%)  2
Respiratory, thoracic and mediastinal disorders     
Cough † 1  4/46 (8.70%)  4 6/45 (13.33%)  8
Dyspnea † 1  6/46 (13.04%)  8 4/45 (8.89%)  4
Pneumonitis † 1  0/46 (0.00%)  0 3/45 (6.67%)  3
Skin and subcutaneous tissue disorders     
Pruritus † 1  2/46 (4.35%)  3 5/45 (11.11%)  7
Rash acneiform † 1  0/46 (0.00%)  0 4/45 (8.89%)  5
Rash maculo-papular † 1  2/46 (4.35%)  2 6/45 (13.33%)  8
Other: Rash † 1  5/46 (10.87%)  7 5/45 (11.11%)  7
Vascular disorders     
Hot flashes † 1  3/46 (6.52%)  4 4/45 (8.89%)  4
Hypertension † 1  6/46 (13.04%)  12 5/45 (11.11%)  12
1
Term from vocabulary, CTCAE 5.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Regulatory Lead
Organization: University of Pennsylvania
Phone: 215-662-4484
EMail: psom-ind-ide@pobox.upenn.edu
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03404960    
Other Study ID Numbers: 828516
First Submitted: December 19, 2017
First Posted: January 19, 2018
Results First Submitted: May 9, 2023
Results First Posted: July 3, 2023
Last Update Posted: March 26, 2024