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A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes (LODESTAR)

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ClinicalTrials.gov Identifier: NCT04171700
Recruitment Status : Terminated (The study was terminated due to a change in development priorities.)
First Posted : November 21, 2019
Results First Posted : October 2, 2023
Last Update Posted : October 2, 2023
Sponsor:
Information provided by (Responsible Party):
pharmaand GmbH

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumor
Intervention Drug: Rucaparib
Enrollment 83
Recruitment Details

A total of 83 participants were enrolled across 19 US sites between January 2020 and March 2022. 63 participants were enrolled in cohort A and 20 in cohort B.

Cohort A comprised participants with a deleterious mutation in one of the following genes; BRCA1, BRCA2, PALB2, RAD51C, RAD51D.

Cohort B comprised participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, RAD51B.
Pre-assignment Details  
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Period Title: Overall Study
Started 63 20
Completed 63 20
Not Completed 0 0
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B Total
Hide Arm/Group Description Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B. Total of all reporting groups
Overall Number of Baseline Participants 63 20 83
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 20 participants 83 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
33
  52.4%
8
  40.0%
41
  49.4%
>=65 years
30
  47.6%
12
  60.0%
42
  50.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants 20 participants 83 participants
64.7  (10.85) 65.2  (13.38) 64.8  (11.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 20 participants 83 participants
Female
36
  57.1%
14
  70.0%
50
  60.2%
Male
27
  42.9%
6
  30.0%
33
  39.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 20 participants 83 participants
Hispanic or Latino
2
   3.2%
0
   0.0%
2
   2.4%
Not Hispanic or Latino
61
  96.8%
20
 100.0%
81
  97.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants 20 participants 83 participants
American Indian or Alaska Native
1
   1.6%
0
   0.0%
1
   1.2%
Asian
1
   1.6%
1
   5.0%
2
   2.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   7.9%
0
   0.0%
5
   6.0%
White
56
  88.9%
19
  95.0%
75
  90.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 63 participants 20 participants 83 participants
63 20 83
1.Primary Outcome
Title Best Overall Response Rate by Investigator
Hide Description Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population - all participants evaluable for response by RECIST v1.1 (or modified RECIST v1.1/PCWG3 for mCRPC participants).
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 61 20
Measure Type: Count of Participants
Unit of Measure: Participants
9
  14.8%
2
  10.0%
2.Secondary Outcome
Title Overall Response Rate by Independent Radiology Review
Hide Description Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
No data were collected as the independent radiology review was not performed.
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Duration of Response
Hide Description Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population - all participants evaluable for response by RECIST v1.1 (or modified RECIST v1.1/PCWG3 for mCRPC participants).
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BRD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 9 2
Median (95% Confidence Interval)
Unit of Measure: month
4.1 [1] 
(3.1 to NA)
6.8
(2.6 to 10.9)
[1]
Insufficient number of participants with events.
4.Secondary Outcome
Title Disease Control Rate
Hide Description Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population - all participants evaluable for response by RECIST v1.1 (or modified RECIST v1.1/PCWG3 for mCRPC participants).
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 61 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
36.1
(24.2 to 49.4)
25.0
(8.7 to 49.1)
5.Secondary Outcome
Title Progression-free Survival
Hide Description Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression. Progression was defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (and an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or the appearance of new lesions. For mCRPC disease, the PCWG3 confirmed bone disease progression criteria (2+2) were also incorporated.
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - all enrolled participants who received at least 1 dose of protocol-specified treatment.
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 63 20
Median (95% Confidence Interval)
Unit of Measure: month
3.7
(1.9 to 5.4)
3.6
(1.6 to 6.3)
6.Secondary Outcome
Title Overall Survival
Hide Description Measure of clinical benefit, defined as the duration from study enrollment to death.
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - all enrolled participants who received at least 1 dose of protocol-specified treatment.
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 63 20
Median (95% Confidence Interval)
Unit of Measure: month
13.3 [1] 
(10.6 to NA)
8.0
(4.8 to 16.6)
[1]
Insufficient number of participants with events.
7.Secondary Outcome
Title Number of Participants Experiencing Treatment-emergent Adverse Events
Hide Description [Not Specified]
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population - all enrolled participants who received at least 1 dose of protocol-specified treatment.
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 63 20
Measure Type: Count of Participants
Unit of Measure: Participants
63
 100.0%
20
 100.0%
8.Secondary Outcome
Title Steady State Minimum Concentration [Cmin]
Hide Description Rucaparib pharmacokinetics
Time Frame From first dose of study drug until disease progression (up to approximately 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics data not collected due to early study termination.
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description:
Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse event data was collected from the date of first dose of study drug until 28 days after the last dose of study drug, approximately 2 years.
Adverse Event Reporting Description Adverse events are reported for the Safety Population, defined as participants who received at least one dose of protocol-specified treatment.
 
Arm/Group Title Rucaparib Cohort A Rucaparib Cohort B
Hide Arm/Group Description Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.
All-Cause Mortality
Rucaparib Cohort A Rucaparib Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   23/63 (36.51%)   10/20 (50.00%) 
Hide Serious Adverse Events
Rucaparib Cohort A Rucaparib Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   13/63 (20.63%)   5/20 (25.00%) 
Blood and lymphatic system disorders     
Anemia † 1  3/63 (4.76%)  0/20 (0.00%) 
Pancytopenia † 1  1/63 (1.59%)  0/20 (0.00%) 
Thrombocytopenia † 1  1/63 (1.59%)  0/20 (0.00%) 
Cardiac disorders     
Cardiac arrest † 1  1/63 (1.59%)  1/20 (5.00%) 
Cardiac failure † 1  0/63 (0.00%)  1/20 (5.00%) 
Gastrointestinal disorders     
Abdominal distension † 1  1/63 (1.59%)  0/20 (0.00%) 
Ascites † 1  1/63 (1.59%)  0/20 (0.00%) 
Constipation † 1  0/63 (0.00%)  1/20 (5.00%) 
Large intestinal obstruction † 1  1/63 (1.59%)  0/20 (0.00%) 
Nausea † 1  1/63 (1.59%)  0/20 (0.00%) 
Obstruction gastric † 1  1/63 (1.59%)  0/20 (0.00%) 
Proctalgia † 1  1/63 (1.59%)  0/20 (0.00%) 
General disorders     
Fatigue † 1  1/63 (1.59%)  0/20 (0.00%) 
Hepatobiliary disorders     
Hepatic failure † 1  1/63 (1.59%)  0/20 (0.00%) 
Infections and infestations     
Pneumonia † 1  1/63 (1.59%)  0/20 (0.00%) 
Metabolism and nutrition disorders     
Hyperkalemia † 1  1/63 (1.59%)  0/20 (0.00%) 
Hypoglycemia † 1  2/63 (3.17%)  0/20 (0.00%) 
Hypokalemia † 1  1/63 (1.59%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  0/63 (0.00%)  1/20 (5.00%) 
Nervous system disorders     
Headache † 1  1/63 (1.59%)  0/20 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  2/63 (3.17%)  0/20 (0.00%) 
Haematuria † 1  1/63 (1.59%)  0/20 (0.00%) 
Renal failure † 1  1/63 (1.59%)  0/20 (0.00%) 
Vascular disorders     
Embolism † 1  0/63 (0.00%)  1/20 (5.00%) 
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Rucaparib Cohort A Rucaparib Cohort B
Affected / at Risk (%) Affected / at Risk (%)
Total   63/63 (100.00%)   19/20 (95.00%) 
Blood and lymphatic system disorders     
Anemia † 1  20/63 (31.75%)  5/20 (25.00%) 
Thrombocytopenia † 1  3/63 (4.76%)  0/20 (0.00%) 
Cardiac disorders     
Bradycardia † 1  2/63 (3.17%)  1/20 (5.00%) 
Gastrointestinal disorders     
Abdominal distension † 1  4/63 (6.35%)  1/20 (5.00%) 
Abdominal pain † 1  7/63 (11.11%)  4/20 (20.00%) 
Abdominal pain upper † 1  3/63 (4.76%)  1/20 (5.00%) 
Constipation † 1  12/63 (19.05%)  2/20 (10.00%) 
Diarrhoea † 1  23/63 (36.51%)  2/20 (10.00%) 
Dyspepsia † 1  4/63 (6.35%)  0/20 (0.00%) 
Nausea † 1  25/63 (39.68%)  8/20 (40.00%) 
Stomatitis † 1  2/63 (3.17%)  1/20 (5.00%) 
Vomiting † 1  18/63 (28.57%)  5/20 (25.00%) 
General disorders     
Chills † 1  3/63 (4.76%)  0/20 (0.00%) 
Fatigue † 1  31/63 (49.21%)  10/20 (50.00%) 
Oedema peripheral † 1  6/63 (9.52%)  2/20 (10.00%) 
Pyrexia † 1  6/63 (9.52%)  0/20 (0.00%) 
Infections and infestations     
COVID-19 † 1  5/63 (7.94%)  0/20 (0.00%) 
Pneumonia † 1  2/63 (3.17%)  1/20 (5.00%) 
Urinary tract infection † 1  7/63 (11.11%)  0/20 (0.00%) 
Injury, poisoning and procedural complications     
Fall † 1  4/63 (6.35%)  0/20 (0.00%) 
Investigations     
Alanine aminotransferase increased † 1  10/63 (15.87%)  2/20 (10.00%) 
Aspartate aminotransferase increased † 1  7/63 (11.11%)  1/20 (5.00%) 
Blood alkaline phosphatase increased † 1  5/63 (7.94%)  0/20 (0.00%) 
Blood bilirubin increased † 1  4/63 (6.35%)  0/20 (0.00%) 
Blood cholesterol increased † 1  2/63 (3.17%)  1/20 (5.00%) 
Blood creatinine increased † 1  7/63 (11.11%)  2/20 (10.00%) 
Blood lactate dehydrogenase increased † 1  3/63 (4.76%)  0/20 (0.00%) 
International normalized ratio increased † 1  3/63 (4.76%)  0/20 (0.00%) 
Lymphocyte count decreased † 1  8/63 (12.70%)  0/20 (0.00%) 
Neutrophil count decreased † 1  10/63 (15.87%)  2/20 (10.00%) 
Platelet count decreased † 1  7/63 (11.11%)  3/20 (15.00%) 
Weight decreased † 1  6/63 (9.52%)  1/20 (5.00%) 
Weight increased † 1  1/63 (1.59%)  2/20 (10.00%) 
White blood cell count decreased † 1  10/63 (15.87%)  1/20 (5.00%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  15/63 (23.81%)  4/20 (20.00%) 
Dehydration † 1  7/63 (11.11%)  4/20 (20.00%) 
Hyperglycemia † 1  4/63 (6.35%)  0/20 (0.00%) 
Hyperkalemia † 1  4/63 (6.35%)  0/20 (0.00%) 
Hypertriglyceridaemia † 1  4/63 (6.35%)  1/20 (5.00%) 
Hypoalbuminaemia † 1  4/63 (6.35%)  0/20 (0.00%) 
Hypokalemia † 1  7/63 (11.11%)  0/20 (0.00%) 
Hypomagnesaemia † 1  6/63 (9.52%)  1/20 (5.00%) 
Hyponatremia † 1  6/63 (9.52%)  0/20 (0.00%) 
Hypophosphataemia † 1  5/63 (7.94%)  0/20 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  6/63 (9.52%)  3/20 (15.00%) 
Back pain † 1  6/63 (9.52%)  1/20 (5.00%) 
Muscular weakness † 1  4/63 (6.35%)  0/20 (0.00%) 
Musculoskeletal chest pain † 1  2/63 (3.17%)  1/20 (5.00%) 
Myalgia † 1  3/63 (4.76%)  1/20 (5.00%) 
Pain in extremity † 1  0/63 (0.00%)  3/20 (15.00%) 
Nervous system disorders     
Dizziness † 1  11/63 (17.46%)  1/20 (5.00%) 
Dysguesia † 1  8/63 (12.70%)  5/20 (25.00%) 
Headache † 1  6/63 (9.52%)  3/20 (15.00%) 
Lethargy † 1  3/63 (4.76%)  1/20 (5.00%) 
Tremor † 1  4/63 (6.35%)  0/20 (0.00%) 
Psychiatric disorders     
Insomnia † 1  3/63 (4.76%)  1/20 (5.00%) 
Renal and urinary disorders     
Chromaturia † 1  2/63 (3.17%)  1/20 (5.00%) 
Hematuria † 1  4/63 (6.35%)  1/20 (5.00%) 
Proteinuria † 1  4/63 (6.35%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  9/63 (14.29%)  1/20 (5.00%) 
Dyspnoea † 1  7/63 (11.11%)  0/20 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  3/63 (4.76%)  2/20 (10.00%) 
Dry skin † 1  3/63 (4.76%)  1/20 (5.00%) 
Pruritis † 1  3/63 (4.76%)  0/20 (0.00%) 
Vascular disorders     
Hypertension † 1  4/63 (6.35%)  0/20 (0.00%) 
Hypotension † 1  3/63 (4.76%)  2/20 (10.00%) 
1
Term from vocabulary, MedDRA 25.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kim Reiss Binder
Organization: University of Pennsylvania
Phone: 1 215 360 0735
EMail: Kim.ReissBinder@uphs.upenn.edu
Layout table for additonal information
Responsible Party: pharmaand GmbH
ClinicalTrials.gov Identifier: NCT04171700    
Other Study ID Numbers: CO-338-100
First Submitted: November 19, 2019
First Posted: November 21, 2019
Results First Submitted: May 31, 2023
Results First Posted: October 2, 2023
Last Update Posted: October 2, 2023