A Randomised Trial of ATRA in a Novel Drug Combination for Pancreatic Cancer

NCT04241276 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 274948
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-centre, randomised, stratified, phase IIb clinical trial of ATRA administered in combination with gemcitabine and nab-paclitaxel in patients with laPDAC.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• To assess the efficacy of ATRA when given in combination with gemcitabine and nab-paclitaxel based on progression free survival (PFS).

  PFS defined as the time from the date of randomisation to the date of first documented tumour progression or death from any cause, whichever occurs first.

  Assessed 8 weekly until progression or death or end of trial, whichever comes first

Secondary Outcomes (6)

• To assess the efficacy of ATRA when given in combination with gemcitabine and nab-paclitaxel based on objective response rate (ORR).

  Assessed 8 weekly until progression or death or end of trial, whichever comes first

• To assess the efficacy of ATRA when given in combination with gemcitabine and nab-paclitaxel based on overall survival (OS).

  Assessed 8 weekly until progression or death and then 3 monthly for at least 12 months after the last safety visit

• To assess the safety and tolerability of ATRA when given in combination with gemcitabine and nab-paclitaxel over the first 6 cycles.

  6 cycles (1 cycle = 28 days)

• To assess the surgical resection rate of ATRA when given in combination with gemcitabine and nab-paclitaxel.

  From consent to at least 12 months after the last safety visit, but further if required as per physician decision - through study completion

• To assess the resection margin negative (R0) surgical resection rate of ATRA when given in combination with gemcitabine and nab-paclitaxel.

  From consent to at least 12 months after the last safety visit, but further if required as per physician decision - through study completion

Study Arms (2)

Gemcitabine + nab-paclitaxel

ACTIVE COMPARATOR

Patients will receive Gemcitabine and nab-Paclitaxel in 28 day cycles until disease progression.

Drug: Gemcitabine; Drug: nab-paclitaxel

Gemcitabine + nab-paclitaxel + ATRA

EXPERIMENTAL

Patients will receive ATRA, Gemcitabine and nab-Paclitaxel in 28 day cycles. ATRA will be administered for 6 cycles whereas Gemcitabine/nab-Paclitaxel will be administered until disease progression.

Drug: ATRA; Drug: Gemcitabine; Drug: nab-paclitaxel

Interventions

ATRA DRUG

45 mg/m2 orally (in two divided doses) from days 1 to 15 of each cycle

Also known as: Tretinoin, Vesanoid

Gemcitabine + nab-paclitaxel + ATRA

Gemcitabine DRUG

1000mg/m2 IV on days 1, 8 and 15 of a 28 day cycle

Gemcitabine + nab-paclitaxel; Gemcitabine + nab-paclitaxel + ATRA

nab-paclitaxel DRUG

125mg/m2 IV on days 1, 8 and 15 of a 28 day cycle

Also known as: Abraxane

Gemcitabine + nab-paclitaxel; Gemcitabine + nab-paclitaxel + ATRA

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent prior to admission to this study
• Age ≥16 years. No upper age limit.
• ECOG performance status 0 or 1
• Histologically proven pancreatic ductal adenocarcinoma (PDAC) as part of the Precision-Panc Master Protocol, or for patients who have gone exploratory laparotomy and found to have locally, unresectable advanced disease.
• Locally advanced disease which is measurable according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1).
• CT chest abdomen and pelvis as well as PET-CT within 28 days of day 1 of treatment (MRI Liver only if indeterminate liver lesions) to confirm absence of metastatic disease.
• Received no prior systemic therapy for pancreatic cancer.
• Adequate haematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:
• Absolute Neutrophil Count ≥ 1.5 x 109/l (without granulocyte colony-stimulating factor support within 2 weeks prior to the first study treatment)
• Platelet count ≥ 100 x 109/l (without transfusion within 2 weeks prior to the first study treatment)
• Haemoglobin ≥ 10 g/dl (transfusion permitted to establish target haemoglobin levels prior to the first study treatment)
• Calculated creatinine clearance (e.g. Cockcroft-Gault) ≥ 50 ml/min
• Bilirubin level ≤ 1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤ 3 x ULN may be enrolled). Patients must be able to undergo biliary stenting if required before or, if required, during the trial
• AST or ALT \<2.5 x ULN
• Alkaline phosphatase (ALP) \<2.5 x ULN

You may not qualify if:

• Patient has known distant metastases.
• Patient has experienced a significant reduction in performance status between the screening/ baseline visit and within 72 hours prior to commencement of treatment as per trial protocol, such that the ECOG PS is ≥ 2 as per the Investigator's assessment.
• Patients with pre-existing sensory neuropathy \>grade 1
• History of other malignancies (except cured basal or squamous cell carcinoma, superficial bladder cancer, prostate cancer in active surveillance, or carcinoma in situ of the cervix) unless documented free of cancer for ≥2 years
• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Patient has known active, uncontrolled HIV, or active, uncontrolled hepatitis B or C infection. Patients with undetectable viral load are eligible.
• Patient has undergone major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
• Patient has a history of allergy (including soya bean or peanut allergies) or hypersensitivity to any of the study drugs or any of their excipients, or the patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of the products or comparator SmPC or Prescribing Information.
• History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
• Patient with a history of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• Patient with high cardiovascular risk , including, but not limited to, recent coronary stenting or myocardial infarction in the past year.
• History of Peripheral Artery Disease (e.g., claudication, Leo-Buerger's disease).
• Patient has serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the patient's safety or the study data integrity.
• Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug at least ≤30 days prior to study entry depending on the half-life of the investigational drug and/or guidance issued by the IMP manufacturer.
• Patient is taking any prohibited concurrent medication, including vitamin A supplements, and is unwilling to stop use prior to and during the trial.

Sponsors & Collaborators

• Medical Research Council: collaborator
• Celgene: collaborator
• Queen Mary University of London: lead

Study Sites (1)

Barts NHS Trust

London, United Kingdom

Location

Related Publications (1)

• Kocher HM; BCI-STARPAC2 team; BPTB team; Precision-Panc team; Sasieni P, Corrie P, McNamara MG, Sarker D, Froeling FEM, Christie A, Gillmore R, Khan K, Propper D. Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2. BMC Cancer. 2025 Jan 20;25(1):106. doi: 10.1186/s12885-024-13333-z.

  PMID: 39833722 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Tretinoin; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Hemant Kocher, Professor

  Queen Mary University of London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 27, 2020
• Study Start: April 30, 2020
• Primary Completion (Estimated): June 29, 2028
• Study Completion (Estimated): February 28, 2029
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)