Trial Outcomes & Findings for Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer (NCT NCT03337087)
NCT ID: NCT03337087
Last Updated: 2024-05-17
Results Overview
Will be assessed to determine maximum tolerated dose (MTD) of the combination of liposomal irinotecan (nal-IRI) and fluorouracil (5FU) with rucaparib (MFR). MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Up to 28 days from start of treatment
Results posted on
2024-05-17
Participant Flow
Participant milestones
| Measure |
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
PHASE Ia: Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\> \> PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\>
\> Fluorouracil: Given IV\>
\> Irinotecan Sucrosofate: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Leucovorin Calcium: Given IV\>
\> Rucaparib: Given PO
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
n=18 Participants
PHASE Ia: Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\> \> PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\>
\> Fluorouracil: Given IV\>
\> Irinotecan Sucrosofate: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Leucovorin Calcium: Given IV\>
\> Rucaparib: Given PO
|
|---|---|
|
Age, Continuous
|
55.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
All Other
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 Participants
n=5 Participants
|
|
ECOG Performance Status
0
|
6 Participants
n=5 Participants
|
|
ECOG Performance Status
1
|
12 Participants
n=5 Participants
|
|
Histologic grade (differentiation)
G1 (Well differentiated)
|
1 Participants
n=5 Participants
|
|
Histologic grade (differentiation)
G2 (Moderately differentiated)
|
9 Participants
n=5 Participants
|
|
Histologic grade (differentiation)
G3 (Poorly differentiated)
|
2 Participants
n=5 Participants
|
|
Histologic grade (differentiation)
GX (Grade cannot be assessed)
|
6 Participants
n=5 Participants
|
|
Number of Metastatic Sites
1
|
6 Participants
n=5 Participants
|
|
Number of Metastatic Sites
2
|
6 Participants
n=5 Participants
|
|
Number of Metastatic Sites
3+
|
6 Participants
n=5 Participants
|
|
Cancer Type
Colorectal
|
11 Participants
n=5 Participants
|
|
Cancer Type
Gastroesophageal
|
1 Participants
n=5 Participants
|
|
Cancer Type
Pancreatic
|
6 Participants
n=5 Participants
|
|
Prior Systemic Therapies in Metastatic Setting
0
|
5 Participants
n=5 Participants
|
|
Prior Systemic Therapies in Metastatic Setting
1
|
2 Participants
n=5 Participants
|
|
Prior Systemic Therapies in Metastatic Setting
2
|
7 Participants
n=5 Participants
|
|
Prior Systemic Therapies in Metastatic Setting
3
|
3 Participants
n=5 Participants
|
|
Prior Systemic Therapies in Metastatic Setting
4+
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 28 days from start of treatmentWill be assessed to determine maximum tolerated dose (MTD) of the combination of liposomal irinotecan (nal-IRI) and fluorouracil (5FU) with rucaparib (MFR). MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.
Outcome measures
| Measure |
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
n=12 Participants
PHASE Ia: Patients receive liposomal irinotecan IV over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\> \> PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.\>
\> Fluorouracil: Given IV\>
\> Irinotecan Sucrosofate: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Leucovorin Calcium: Given IV\>
\> Rucaparib: Given PO
|
|---|---|
|
Number of Participants With Dose Limiting Toxicities (Phase I)
|
1 Participants
|
Adverse Events
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
Serious events: 15 serious events
Other events: 18 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
n=18 participants at risk
Rucaparib: Given PO
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
22.2%
4/18 • Number of events 6 • Up to 3 years
|
|
Gastrointestinal disorders
Colonic obstruction
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
16.7%
3/18 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Oth spec
|
11.1%
2/18 • Number of events 2 • Up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
16.7%
3/18 • Number of events 4 • Up to 3 years
|
|
Gastrointestinal disorders
Obstruction gastric
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Rectal pain
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
General disorders
Fatigue
|
11.1%
2/18 • Number of events 3 • Up to 3 years
|
|
General disorders
Fever
|
16.7%
3/18 • Number of events 4 • Up to 3 years
|
|
General disorders
Multi-organ failure
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Infections and infestations
Device related infection
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
16.7%
3/18 • Number of events 4 • Up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Investigations
Creatinine increased
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Investigations
Lymphocyte count decreased
|
16.7%
3/18 • Number of events 3 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
22.2%
4/18 • Number of events 4 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
5.6%
1/18 • Number of events 2 • Up to 3 years
|
|
Investigations
White blood cell decreased
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
5.6%
1/18 • Number of events 2 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Vascular disorders
Thromboembolic event
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
Other adverse events
| Measure |
Treatment (Nal-IRI, Leucovorin, Fluorouracil, Rucaparib)
n=18 participants at risk
Rucaparib: Given PO
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
66.7%
12/18 • Number of events 51 • Up to 3 years
|
|
Blood and lymphatic system disorders
Blood and lymph sys disorders - Oth Spec
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Eye disorders
Blurred vision
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Eye disorders
Dry eye
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Eye disorders
Periorbital edema
|
5.6%
1/18 • Number of events 2 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
3/18 • Number of events 4 • Up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
11.1%
2/18 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
72.2%
13/18 • Number of events 66 • Up to 3 years
|
|
Gastrointestinal disorders
Flatulence
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Oth spec
|
11.1%
2/18 • Number of events 6 • Up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal fistula
|
5.6%
1/18 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
16.7%
3/18 • Number of events 3 • Up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
72.2%
13/18 • Number of events 55 • Up to 3 years
|
|
Gastrointestinal disorders
Oral pain
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
38.9%
7/18 • Number of events 20 • Up to 3 years
|
|
General disorders
Edema face
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
General disorders
Edema limbs
|
33.3%
6/18 • Number of events 8 • Up to 3 years
|
|
General disorders
Fatigue
|
66.7%
12/18 • Number of events 91 • Up to 3 years
|
|
General disorders
Gen disord and admin site conds-Oth spec
|
5.6%
1/18 • Number of events 2 • Up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
44.4%
8/18 • Number of events 24 • Up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
83.3%
15/18 • Number of events 65 • Up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
44.4%
8/18 • Number of events 23 • Up to 3 years
|
|
Investigations
Blood bilirubin increased
|
27.8%
5/18 • Number of events 11 • Up to 3 years
|
|
Investigations
Creatinine increased
|
22.2%
4/18 • Number of events 7 • Up to 3 years
|
|
Investigations
Lymphocyte count decreased
|
44.4%
8/18 • Number of events 50 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
61.1%
11/18 • Number of events 23 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
50.0%
9/18 • Number of events 31 • Up to 3 years
|
|
Investigations
Weight loss
|
16.7%
3/18 • Number of events 3 • Up to 3 years
|
|
Investigations
White blood cell decreased
|
61.1%
11/18 • Number of events 17 • Up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
22.2%
4/18 • Number of events 6 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
3/18 • Number of events 5 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
11.1%
2/18 • Number of events 2 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
16.7%
3/18 • Number of events 9 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
66.7%
12/18 • Number of events 27 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Dizziness
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Dysgeusia
|
5.6%
1/18 • Number of events 5 • Up to 3 years
|
|
Nervous system disorders
Headache
|
16.7%
3/18 • Number of events 5 • Up to 3 years
|
|
Nervous system disorders
Paresthesia
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Resp, thoracic, mediastinal - Oth spec
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
27.8%
5/18 • Number of events 14 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.6%
1/18 • Number of events 1 • Up to 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place