This study is to understand how well an investigational drug (called Napabucasin) works when given in combination with chemotherapy treatment for people with pancreatic cancer after prior chemotherapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

1globe Health Institute LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 May 2022 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

1Globe Health Institute

External identifiers

EU CT number

2024-518205-17-00

EudraCT number

2019-002553-35

ClinicalTrials.gov

NCT03721744

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacogenomic, Pharmacokinetic, Pharmacogenetic, Safety, Efficacy, Pharmacodynamic, Therapy

To compare the following endpoints for napabucasin in combination with weekly paclitaxel and low-dose gemcitabine (Arm 1) versus standard of care treatment options (Arm 2) in patients with metastatic pancreatic adenocarcinoma following chemotherapy failure:

Phase II part of the study:
 Progression free survival (PFS)
 Safety


Phase III part of the study:
 Overall survival (OS)

Note: Overall survival will not be assessed in Phase II part of this study. Phase II patients will be pooled with Phase III patients for Phase III assessment of OS.

Secondary objectives 7

1. Phase II part of the study: Disease control rate (DCR)
2. Phase II part of the study: Objective response rate (ORR)
3. Phase III part of the study: PFS
4. Phase III part of the study: ORR and DCR
5. Phase III part of the study: OS, PFS, ORR and DCR in the predefined biomarker-positive sub-population
6. Phase III part of the study: Safety
7. Phase III part of the study: Quality of life (QoL)

Conditions and MedDRA coding

Histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is metastatic.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Written, signed consent for trial participation must be obtained from the patient appropriately in accordance with applicable ICH guidelines and local and regulatory requirements.
2. Must have histologically or cytologically confirmed advanced pancreatic adenocarcinoma that is metastatic.
3. Must have failed at least one line of chemotherapy, including but not limited to: •A gemcitabine-containing regimen (i.e. single-agent or in combination); •FOLFIRINOX or mFOLFIRINOX. Patients who are candidates for and have access to gemcitabine-nab-paclitaxel or are candidates for FOLFIRINOX/mFOLFIRINOX must have received these standard of care regimens before randomization. Patients who relapsed during or within 6 months of last dose of the regimens listed above in the adjuvant or neoadjuvant setting may be enrolled.
4. Must have one or more metastatic tumors evaluable by CT scan with contrast (or MRI, if patient is allergic to CT contrast media) per RECIST 1.1. Imaging investigations including CT/MRI of chest/abdomen/pelvis or other scans as necessary to document all sites of disease must be performed within 14 days prior to randomization. Qualifying scans performed as part of standard of care prior to patient signature of the study informed consent will be acceptable as baseline scanning as long as scanning is performed ≤ 14 days prior to randomization.
5. Must have ECOG Performance Status of 0 or 1, assessed within 14 days prior to randomization
6. Must have life-expectancy of > 12 weeks.
7. Must be ≥ 18 years of age.
8. For male or female patients of child producing potential: must agree to use contraception or take measures to avoid pregnancy during the study and for 180 days after the final dose of the chemotherapy or for 30 days for female patients and for 90 days for male patients, after the final napabucasin dose if chemotherapy were not administered.
9. Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 3 days prior to randomization.
10. Patient has adequate biological parameters as demonstrated by the following blood counts at baseline (obtained ≤ 14 days prior to randomization: •Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; •Platelet count ≥ 100,000/mm3 (100 × 109/L); •Hemoglobin (Hgb) ≥ 9 g/dL.
11. Patient has the following blood chemistry levels at baseline (obtained ≤ 14 days prior to randomization: •AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN) [5 ×ULN in presence of liver metastases]; •Total bilirubin ≤ 1.5 × institutional ULN. If total bilirubin is > ULN, it must be non-rising for at least 3 days; •Serum creatinine within normal limits or calculated clearance > 60 mL/min/1.73 m2 for patients with serum creatinine levels above or below the institutional normal value.
12. Patient not on anticoagulation has acceptable coagulation studies (obtained ≤ 14 days prior to randomization as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) below or within normal limits (+15%).
13. Patient has no clinically significant abnormalities on urinalysis results (obtained ≤ 14 days prior to randomization).
14. Patient must have adequate nutritional status with Body Mass Index (BMI) ≥ 18 kg/m2 and body weight of ≥ 40 kg with serum albumin ≥ 3 g/dL.
15. Patients requiring biliary stent placement must have biliary stent placed ≥ 7 days prior to screening.
16. Pain symptoms should be stable (of tolerable Grade 2 or less).
17. Only patients with available archival tumor tissue must consent to provision of, and Investigator(s) must confirm access to and agree to submit a representative formalin fixed paraffin block of tumor tissue in order that the specific correlative marker assays proscribed in this protocol may be conducted.
18. Patients must be accessible for treatment and follow-up.
19. The patient is not receiving therapy in a concurrent clinical study and the patient agrees not to participate in other interventional clinical studies during their participation in this trial while on study treatment.

Exclusion criteria 24

1. Anti-cancer chemotherapy, radiotherapy, biologic therapy or immunotherapy/immunomodulating treatment (for non-cancer related treatment) administered two weeks prior to the first planned dose of study medication. Investigational agents administered within four weeks of first planned dose of study medication. An exception is made for oral fluoropyrimidines (e.g. capecitabine, S-1), where a minimum of 10 days since last dose must be observed prior to the first planned dose of study medication.
2. Patients with any unresolved lingering toxicity > Grade 2 from prior treatment will be excluded.
3. Patients received prior chemotherapy only in the adjuvant or neoadjuvant setting, with progression occurring > 6 months of completion of therapy or resection with curative intent, respectively.
4. Patients who were intolerant to prior taxane treatment.
5. Patient has experienced a decline in ECOG performance status between baseline visit and within 3 days prior to randomization.
6. Patient has a ≥ 20% decrease in serum albumin level between baseline visit and within 3 days prior to randomization.
7. Patient has a ≥ 10% decrease in weight between baseline visit and within 3 days prior to randomization.
8. Major surgery within 4 weeks prior to randomization.
9. Patients with any known brain or leptomeningeal metastases are excluded, even if treated.
10. Patients with clinically significant pleural effusion or ascites.
11. Women who are pregnant or breastfeeding.
12. Patients with gastrointestinal disorder(s) which could significantly impede the absorption of an oral agent.
13. Prior treatment with napabucasin or participation in a clinical trial evaluating napabucasin.
14. Unable or unwilling to swallow napabucasin capsules daily.
15. Patient who has smoked cigarettes/tobacco within 28 days prior to randomization or plan to use these products while on study treatment.
16. Uncontrolled inter-current illness.
17. Known hypersensitivity to gemcitabine, taxanes or any of their excipients.
18. Neurosensory neuropathy ≥ grade 2 at baseline.
19. Uncontrolled chronic diarrhea ≥ grade 2 at baseline.
20. Patients being treated with any coumarins.
21. Patients with active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy.
22. Patients with a history of other malignancies.
23. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy.
24. Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase II Part of the Study: Progression Free Survival (PFS)
2. Phase II Part of the Study: Safety in the general study population
3. Phase III Part of the Study: Overall Survival (OS) in the general study population.

Secondary endpoints 7

1. Phase II Part of the Study: •Disease control rate (DCR) in the general study population
2. Phase II Part of the Study: •Objective response rate (ORR) in the general study population
3. Phase III Part of the Study: •PFS in the general study population
4. Phase III Part of the Study: •ORR and DCR in the general study population
5. Phase III Part of the Study: •OS, PFS, ORR and DCR in the predefined biomarker positive population
6. Phase III Part of the Study: •Safety
7. Phase III Part of the Study: •Quality of Life

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

1globe Health Institute LLC

Sponsor organisation

1globe Health Institute LLC

Address

1209 North Orange Street

City

Wilmington

Postcode

19801-1120

Country

United States

Scientific contact point

Organisation

1globe Health Institute LLC

Contact name

STEMNESS Clinical Trial Info

Public contact point

Organisation

1globe Health Institute LLC

Contact name

STEMNESS Clinical Trial Info

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications