NCT02178436

Gemcitabine, Nab-paclitaxel and KPT-330 in Advanced Pancreatic Cancer

Completed Phase 1, PHASE2 Results posted Last updated 7 November 2023

What this trial tests

Phase 1, PHASE2 trial testing gemcitabine hydrochloride in Acinar Cell Adenocarcinoma of the Pancreas in 15 participants. Completed in 5 April 2023.

Timeline

31 October 2014

Primary endpoint
27 November 2021

5 April 2023

Quick facts

Lead sponsor	Mohammed Najeeb Al Hallak
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	31 October 2014
Primary completion	27 November 2021
Estimated completion	5 April 2023
Sites	2 locations across United States

Drugs / interventions tested

• gemcitabine hydrochloride — full drug profile →
• Selinexor — full drug profile →
• Pharmacological Study — full drug profile →
• Laboratory Biomarker Analysis — full drug profile →
• Nab paclitaxel

Conditions studied

• Acinar Cell Adenocarcinoma of the Pancreas — all drugs for Acinar Cell Adenocarcinoma of the Pancreas →
• Duct Cell Adenocarcinoma of the Pancreas — all drugs for Duct Cell Adenocarcinoma of the Pancreas →
• Stage IV Pancreatic Cancer — all drugs for Stage IV Pancreatic Cancer →

Sponsor

Mohammed Najeeb Al Hallak

Who can join

19 and older, any sex, with Acinar Cell Adenocarcinoma of the Pancreas or Duct Cell Adenocarcinoma of the Pancreas. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) of Selinexor, Gemcitabine Hydrochloride, and Paclitaxel Albumin-stabilized Nanoparticle Formulation Combination (Phase Ib) Primary · 28 days

MTD is defined as the lowest dose for which less than a third of patients experience a dose limiting toxicity graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Group	Value	95% CI
Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)	80

Proportion of Patients With a Toxic Event, Graded According to NCI CTCAE Version 4.03 Primary · Up to 2 years

The reported output is the proportion of patients that had a toxic event along with the associated 90% Wilson's confidence interval.

Group	Value	95% CI
Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)	1.00	0.77 – 1.00
GroupIII: Phase II Group II (Gemcitabine, Selinexor)	0.75	0.36 – 0.94

Overall Survival (Phase II) Primary · Up to 7 months post treatment initiation

Estimated on an intention-to-treat basis (using all registered patients), and on a response-evaluable basis (using all patients who completed at least one 4-week treatment cycle) using the Kaplan-Meier method.

Group	Value	95% CI
Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)	5.45	4.37 – NA
GroupIII: Phase II Group II (Gemcitabine, Selinexor)	NA	NA – NA

Proportion of Patients With a Response Secondary · Up to 2 years

Point and 90% Wilson's confidence intervals will be estimated to describe response rate. If the best observed clinical response was complete response or partial response, we consider that the patient responded.

Group	Value	95% CI
Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)	0.40	0.14 – 0.73
GroupIII: Phase II Group II (Gemcitabine, Selinexor)	0	0 – 0.40

Progression Free Survival (Phase II) Secondary · Up to 2 years

Estimated on an intention-to-treat basis (using all registered patients), and on a response-evaluable basis (using all patients who completed at least one 4-week treatment cycle) using the Kaplan-Meier method. Both progression and death are considered events for this analysis.

Group	Value	95% CI
Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)	4.60	4.37 – NA
GroupIII: Phase II Group II (Gemcitabine, Selinexor)	1.74	1.22 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: The adverse events were collected from cycle one day one of study treatment until four weeks follow up visit or thirty days after study treatment was discontinued up to 2 years.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group I: Phase Ib (Gemcitabine, Nab-paclitaxel, Selinexor)

Serious: 6/9 (67%)

Deaths: 9/9

Group II: Phase II Group I (Gemcitabine, Selinexor)

Serious: 0

Deaths: 0

GroupIII: Phase II Group II (Gemcitabine, Selinexor)

Serious: 0/4 (0%)

Deaths: 0/4

Serious adverse events (11 terms)

Reaction	System	Group I: Phase Ib (Gemcita…	Group II: Phase II Group I…	GroupIII: Phase II Group I…
Abdominal Pain	Gastrointestinal disorders	—	—	—
Cognitive disturbance	Nervous system disorders	—	—	—
Death NOS	General disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Hyperglycemia	Investigations	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Psychiatric disorders - Other	Psychiatric disorders	—	—	—
Renal and urinary disorders - Other	Renal and urinary disorders	—	—	—
Stroke	Nervous system disorders	—	—	—
Suicidal ideation	Psychiatric disorders	—	—	—
Suicide attempt	Psychiatric disorders	—	—	—

Other adverse events (70 terms — click to expand)

Reaction	System	Group I: Phase Ib (Gemcita…	Group II: Phase II Group I…	GroupIII: Phase II Group I…
Fatigue	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Anorexia	Gastrointestinal disorders	—	—	—
Dysgeusia	Nervous system disorders	—	—	—
Eye disorders - Other, specify	Eye disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Malaise	General disorders	—	—	—
Neutrophil count decreased	Investigations	—	—	—
Edema limbs	General disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Anxiety	Psychiatric disorders	—	—	—
Blurred vision	Eye disorders	—	—	—
Chills	General disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Depression	Psychiatric disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Musculoskeletal and connective tissue disorder - Other, specify	Metabolism and nutrition disorders	—	—	—
White blood cell decreased	Blood and lymphatic system disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—
Ascites	Gastrointestinal disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Blood bilirubin increased	Investigations	—	—	—
Bruising	Injury, poisoning and procedural complications	—	—	—
Creatinine increased	Investigations	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Ear and labyrinth disorders - Other, specify	Ear and labyrinth disorders	—	—	—
Ear pain	Ear and labyrinth disorders	—	—	—
Flashing lights	Eye disorders	—	—	—
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	—	—	—
General disorders and administration site conditions - Other, specify	General disorders	—	—	—

Most-reported serious reactions: Abdominal Pain, Cognitive disturbance, Death NOS, Headache, Hyperglycemia, Nausea, Psychiatric disorders - Other, Renal and urinary disorders - Other.

Data from ClinicalTrials.gov NCT02178436 adverse events section.

Sponsor's own description

This partially randomized phase Ib/II trial studies the side effects and best dose of selinexor when given together with gemcitabine and nab-paclitaxel, and to see how well they work in treating patients with pancreatic cancer that has spread to other parts of the body (metastatic). Drugs used in chemotherapy, such as selinexor, gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. XPO1-dependent nuclear export as a target for cancer therapy.
   Azizian NG, Li Y. · · 2020 · cited 183× · PMID 32487143 · DOI 10.1186/s13045-020-00903-4
2. The past, present, and future of CRM1/XPO1 inhibitors.
   Wang AY, Liu H. · · 2019 · cited 85× · PMID 30976603 · DOI 10.21037/sci.2019.02.03
3. Metastatic pancreatic cancer: Is there a light at the end of the tunnel?
   Vaccaro V, Sperduti I, Vari S, Bria E, et al · · 2015 · cited 49× · PMID 25944992 · DOI 10.3748/wjg.v21.i16.4788
4. Hacking Pancreatic Cancer: Present and Future of Personalized Medicine.
   Di Federico A, Tateo V, Parisi C, Formica F, et al · · 2021 · cited 48× · PMID 34358103 · DOI 10.3390/ph14070677
5. Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1.
   Luedtke DA, Su Y, Liu S, Edwards H, et al · · 2018 · cited 47× · PMID 30596398 · DOI 10.1111/jcmm.13886
6. Preclinical Assessment with Clinical Validation of Selinexor with Gemcitabine and Nab-Paclitaxel for the Treatment of Pancreatic Ductal Adenocarcinoma.
   Azmi AS, Khan HY, Muqbil I, Aboukameel A, et al · · 2020 · cited 42× · PMID 31831564 · DOI 10.1158/1078-0432.ccr-19-1728
7. Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration.
   Azmi AS, Li Y, Muqbil I, Aboukameel A, et al · · 2017 · cited 40× · PMID 29137251 · DOI 10.18632/oncotarget.19285
8. Protein nanoparticles directed cancer imaging and therapy.
   Miao Y, Yang T, Yang S, Yang M, et al · · 2022 · cited 39× · PMID 34997888 · DOI 10.1186/s40580-021-00293-4