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Pancreatic AdenocarcinomaPhase 1STAR_PACNCT03307148

Stromal TARgeting for PAncreatic Cancer (STAR_PAC)

A Phase 1 study testing ATRA, Gemcitabine and Nab-paclitaxel in people with Pancreatic Adenocarcinoma, run by Barts & The London NHS Trust at 4 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Pancreatic cancer (PDAC) is the fourth highest cancer killer worldwide and is responsible for 6% of cancer deaths. Around 80% of patients are diagnosed at a late stage when cancer has spread and surgical removal is no longer possible. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Adenocarcinoma
What is being tested?
ATRA, Gemcitabine and Nab-paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
4 sitesUnited Kingdom
Study dates
15 Jan 2016to 19 Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must meet all of the following inclusion criteria to be enrolled in the study:
  • Written informed consent prior to admission to this study
  • Age ≥18 years. No upper age limit.
  • WHO performance status 0 or 1
  • Life expectancy ≥12 weeks
  • Histologically proven Pancreatic ductal adenocarcinoma (PDAC). Formalin fixed, paraffin embedded tumour sample from the primary cancer must be available for central testing. If not available or sufficient patients will be asked to undergo an US or CT guided biopsy prior to study entry to satisfy this eligibility criterion.
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  • Locally advanced or metastatic disease which is measurable according to the Response Evaluation Criteria in Solid Tumours (RECIST v1.1)
  • Received no prior systemic therapy for metastatic or locally advanced disease. Prior adjuvant chemotherapy (with Gemcitabine or any other drug/s) is allowed if completed at least 6 months previously.
  • Adequate hematologic 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 or <5 x ULN in the presence of liver metastases
  • Alkaline phosphatase (ALP) <2.5 x ULN or <5 x ULN in the presence of liver and/or bone metastases
  • INR and aPTT ≤1.5 x ULN; this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Female patients of child-bearing potential are eligible, provided they have a negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment, preferably as close to the first dose as possible. All patients with reproductive potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 1 month after discontinuation of ATRA and / or Gemcitabine/nab-Paclitaxel (whichever is the latest) and for 6 months after discontinuation for male patients. Acceptable methods of contraception include IUD, oral contraceptive, sub-dermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary). Micro-dosed progesterone preparations ("mini-pill") are an inadequate method of contraception during treatment with ATRA. If patients are taking this pill they should be instructed to stop and another form of contraceptive should be prescribed instead.
  • Able to follow protocol requirements as assessed by the Principal investigator.

Who cannot join

  • A patient will not be eligible for inclusion in this study if any of the following criteria apply:
  • Patient has known brain 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, and as per the Investigator's assessment.
  • Patients with pre-existing sensory neuropathy >grade 1
  • History of malignancy in the last 5 years, with the exception of:
  • Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
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  • Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 5 years.
  • Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  • Patient has HIV, or active hepatitis B or C infection.
  • 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 ≤ 30 days prior to study entry depending on the half-life of the investigational drug and/or guidance issued by the IMP manufacturer. Please contact the STARPAC Coordinating team for further information.
  • Patient is taking any prohibited concurrent medication, including Vitamin A supplements, and is unwilling to stop use prior to and during the trial. Refer to section 6.11.2.
  • Patient is pregnant, planning to become pregnant or breast feeding.
  • Patient has received a live vaccine within four weeks prior to receiving their first dose of study treatment.
  • Patient is unwilling or unable to comply with study procedures, as assessed by the Principal Investigator.

Trial locations and contacts

4 sites in 1 country.

United Kingdom4 sites

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, CB2 0QQ

  • Barts and The London NHS, St Bartholomew's Hospital

    London, EC1 A 7BE

  • Guy's and St Thomas' NHS Foundation Trust

    London

  • Imperial College NHS Trust

    London

Other trials in United Kingdom

About this study

Official title: A Phase 1B Study Repurposing ATRA as Stromal Targeting Agent Along With Gemcitabine and Nab-Paclitaxel for Pancreatic Cancer (STAR_PAC)

Pancreatic cancer (PDAC) is the fourth highest cancer killer worldwide and is responsible for 6% of cancer deaths. Around 80% of patients are diagnosed at a late stage when cancer has spread and surgical removal is no longer possible. At present there are no treatments available which will shrink the tumour to enable surgical removal.

A main factor in the lack of treatment options for patients is that pancreatic cancer is surrounded by a thick scar tissue called the stroma, which forms a barrier to prevent chemotherapy from entering and shrinking the tumour. Research carried out in laboratories has shown that a derivative of Vitamin A, All Trans Retinoic Acid (ATRA), may have the ability to break down this stroma allowing chemotherapy to reach the cancer.

Read more

STAR_PAC will test the combination of ATRA with two chemotherapy drugs; Gemcitabine and Nab-Paclitaxel in patients with locally advanced or metastatic pancreatic cancer. There are two parts to the study; the first will test different doses of the drugs on around 24 patients to find the highest dose patients can take without too many side effects. The second part will test this dose on around 10 patients to find the dose that will produce the desired effect with limited side effects. Patients will take ATRA for up to 6 cycles and chemotherapy until their cancer worsens and will be followed up for 12 months. The study will also explore the ability of a type of scan, DW-MRI, to detect changes in the cancer (optional for patients). Patients can also opt to donate additional tumour samples (biopsies) and normal cell samples (cheek cells and hair samples).

Eligible patients will be recruited through NHS Clinics and should have histologically confirmed locally advanced or metastatic pancreatic cancer according to RECIST criteria and must have received no prior treatment for this cancer.

Being tested
ATRA, Gemcitabine, Nab-paclitaxel
Keywords
Locally Advanced or Metastatic
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATRADrug

    Also called Tretinoin, Vesanoid

    Administered orally on D1-15 of each 28 day cycle.

  • GemcitabineDrug

    Intravenous Infusion on D1,8 and 15 of each 28 day cycle.

  • Nab-paclitaxelDrug

    Also called Abraxane

    Intravenous Infusion on D1,8 and 15 of each 28 day cycle.

Study groups in NCT03307148
Study groupRoleWhat they receive
ATRA in combination with Gemcitabine and Nab-PaclitaxelExperimentalPatients 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.
Receives: Drug: ATRA; Drug: Gemcitabine; Drug: Nab-paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Dose Limiting Toxicities (DLT)

    Occurrence of DLT which can be attributed as possibly, probably or definitely related to the study treatment.

    Measured: First 28 days of treatment

  2. Part 2: Optimum Biological Dose (OBD)

    Determination of OBD based on serum Vitamin A levels measured at the end of each treatment cycle.

    Measured: Up to 6 cycles of treatment (1 cycle = 28 days)

Secondary outcomes (8)

  1. Maximum concentration observed (Cmax)

    ATRA PK will be assessed predose and post dose up to 5 hours on day 1 of cycles 1-3 to determine the Cmax.

    Measured: Up to 3 cycles (1 cycle = 28 days)

  2. Time of maximum concentration observed (Tmax)

    ATRA PK will be assessed predose and post dose up to 5 hours on day 1 of cycles 1-3 to determine the Tmax.

    Measured: Up to 3 cycles (1 cycle = 28 days)

  3. Area under the curve (AUC)

    ATRA PK will be assessed predose and post dose up to 5 hours on day 1 of cycles 1-3 to determine the AUC.

    Measured: Up to 3 cycles (1 cycle = 28 days)

  4. Change in serum Vitamin A levels

    Change in serum Vitamin A levels relative to baseline at the end of cycles 1 and 2 will be assessed.

    Measured: End of cycles 1 and 2 ( 1 cycle = 28 days).

  5. Incidence of adverse events (AE)

    Incidence of AE (graded by NCI CTCAE v4.03) will be assessed.

    Measured: From time of consent until end of treatment, an average of 8 months.

  6. Objective response rate (ORR)

    The percentage of patients with measurable disease at baseline who have at least one visit response of CR or PR prior to any evidence of progression, as defined by the site radiologist using CT scans (RECIST v1.1).

    Measured: Assessed 8 weekly until progression or death for a maximum of 12 months.

  7. Progression free survival (PFS)

    The time from the date of registration to the date of first documented tumour progression (as assessed by the site radiologist and/or investigator, using RECIST v1.1) or death from any cause, whichever occurs first.

    Measured: Assessed 8 weekly until progression or death for a maximum of 12 months.

  8. Overall survival (OS)

    The time from registration to death from any cause or 12 months follow up, whichever occurs first.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2017
  2. Study start15 Jan 2016
  3. Primary completion19 Mar 2019
  4. Study completion19 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03307148
Sponsor's protocol ID
010432QM
Other IDs
2015-002662-23, 2015
Acronym
STAR_PAC
Status last verified
Jan 2020
First submitted
30 Aug 2017
Last updated
22 Jan 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kocher HM, Basu B, Froeling FEM, Sarker D, Slater S, Carlin D, deSouza NM, De Paepe KN, Goulart MR, Hughes C, Imrali A, Roberts R, Pawula M, Houghton R, Lawrence C, Yogeswaran Y, Mousa K, Coetzee C, Sasieni P, Prendergast A, Propper DJ. Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer. Nat Commun. 2020 Sep 24;11(1):4841. doi: 10.1038/s41467-020-18636-w.

    PubMed 32973176

  • North B, Kocher HM, Sasieni P. A new pragmatic design for dose escalation in phase 1 clinical trials using an adaptive continual reassessment method. BMC Cancer. 2019 Jun 26;19(1):632. doi: 10.1186/s12885-019-5801-3.

    PubMed 31242873

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ATRA, Gemcitabine and Nab-paclitaxel in people with Pancreatic Adenocarcinoma, run by Barts & The London NHS Trust at 4 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Dose Limiting Toxicities (DLT) (time frame: First 28 days of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03307148, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.

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