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Hepatocellular CarcinomaPLANETNCT03267641

Prospective Cohort Study on the Clinical Trajectory of Resected Hepatocellular Carcinoma

An observational study of Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 6 sites in 4 countries.

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

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most important cause of cancer death. Because of its highly heterogeneous nature, the current approach to identifying druggable targets have not delivered efficacious therapies in HCC and is a main reason for the high case fatality. Read more about this study

Who is it for?
Ages 21 to 80 years
Conditions the study is for
Hepatocellular Carcinoma
How many people
86 participants
Where
6 sitesin 4 countries
Study dates
16 May 2016to 31 Mar 2021
Phase
Observational
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 21 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients who have undergone resection of HCC with curative intent with a R0 and R1 resection margin

Who may be able to join

  • Male and female patients, 21 to 80 years of age at the time of signature of the informed consent form.
  • Histologically proven HCC after liver resection. Combined hepatocellular-cholangiocarcinoma can be included.
  • HCC limited to the liver with no extra-hepatic metastasis on CT or MRI of the abdomen and chest (defined as lymph node <2 cm, lung nodules < 1 cm, farther lymph nodes < 2 cm) according to the AASLD criteria65.
  • R0 or R1 resection on histology.
  • Eligibility according to tumour size:
  • Large tumour >= 5 cm (preferred)
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  • Smaller tumours >=2cm and < 5cm
  • Multifocal tumours - maximum of 3 total tumours with size >=2cm detected from CT-scan. Detection of <1cm tumour intra-operatively or upon histologic examination following resection can be ignored. For multiple satellite nodules (>=2cm) that are detected intraoperatively, harvest ALL satellite nodules (>/= 2cm). DNA/RNA will be extracted from cases confirmed to be HCC/hepato-cholangiocarcinoma by histology. A MAXIMUM of 3 samples with the best quality are to be used for the analysis.
  • Child-Pugh ≤ 7 points without clinical ascites before surgery.
  • ECOG performance status 0-1 before surgery.
  • Scheduled for liver resection within 6 weeks.
  • The patient has received no anti-cancer specific treatment for HCC eg. previous liver resection, loco-regional therapy (e.g. RFA, TACE, SIRT), radiotherapy, immunotherapy, chemotherapy or neo-adjuvant chemotherapy other than the planned surgery. However, patient who has received previous HCC resection more than 5 years ago is deemed to have a de-novo liver tumour and therefore can be included.
  • Adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria:
  • Absolute neutrophil count ≥ 1.0 x 10^9/L
  • Platelet count ≥ 50 x 10^9/L
  • Haemoglobin ≥ 9.0 g/dL
  • INR ≤ 2.0
  • Serum creatinine ≤ 1.5 times the Upper Limit of Normal (ULN)
  • Albumin ≥ 2.5 g/dL
  • Total bilirubin ≤ 1.5 times the ULN
  • Alanine transaminase (ALT) ≤ 2.5 times the ULN
  • Aspartate transaminase (AST ≤ 2.5 times the ULN

Who cannot join

  • Single lesion < 2 cm at the time of tumour resection.
  • The patient has previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and highly likely to have been cured.
  • Encephalopathy
  • The patient has received a major organ allograft.
  • The patient is known to be positive for the Human Immunodeficiency Virus (HIV).
  • The patient has an uncontrolled bleeding disorder.
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  • The patient has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or uncontrolled arrhythmia at the time of enrolment.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
  • The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • The patient has received any investigational or non-registered medicinal product (drug or vaccine) within the 30 days preceding the date of enrolment, or plans to receive such a drug during the study period.
  • For female patients: the patient is pregnant or lactating.
  • Insufficient DNA/RNA for genome analysis at baseline
  • Insufficient cells for immunology analysis at baseline (Singapore sites only)

Trial locations and contacts

6 sites in 4 countries.

6 sites in 4 countries

Singapore3 sites

  • National University Hospital

    Singapore, 119228

  • Singapore General Hospital

    Singapore, 169608

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

Malaysia1 site

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

Other trials in Malaysia

Philippines1 site

  • The Medical Centre, Philippines

    Manila, 1605

Other trials in Philippines

Thailand1 site

  • National Cancer Institute Thailand

    Bangkok, 10400

Other trials in Thailand

About this study

Official title: A Multi-National Cohort Study On The Impact Of Intra-Tumoural Genomic Heterogeneity And The Immune Micro-Environment On The Clinical Trajectory Of Resected Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world but the 2nd most important cause of cancer death. Because of its highly heterogeneous nature, the current approach to identifying druggable targets have not delivered efficacious therapies in HCC and is a main reason for the high case fatality. Even when surgical resection is potentially curative in early disease, tumor recurrence remains high and long term survival poor because of the absence of useful adjuvant therapy.

To address these unmet needs, the investigators bring together internationally recognized scientists from genomics and immunology and established clinician investigators in a synergistic team. This TCR capitalizes on recent collaborative advances made by the PIs in the consortium. The investigators have shown through multi-region sampling of freshly resected HCC and phylogenetic analysis, that significant intra-tumoral heterogeneity exists and have identified the specific positions of known clonal drivers. Simultaneously the investigators have analyzed the immune landscape of the tumor microenvironment with deep immune-phenotyping and found unique inter-patient immune landscapes predictive of clinical trajectory.

Read more

This TCR is a prospective study that samples resected HCC from multi-ethnic sites within the established Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group, which has enrolled approximately 1000 patients through 6 multi-center trials in 35 centers in the region. Clinical trajectories are tracked and genomic and immunological studies are repeated when tumors recu r, to confirm clonally dominant driver mutations and immunological processes that are targetable. Concurrently, representative pre-clinical models will be developed from the tissues sampled.

The investigators aim to combine these approaches to overcome the challenges posed by genomic heterogeneity and to guide the development of therapeutics and precision medicine in HCC.

Keywords
Intra-tumour heterogeneity, Cancer immunotherapy, Tumour microenvironment, Driver mutations, Precision Medicine
Medical subject headings
Carcinoma, Hepatocellular

What is being measured

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

  1. Time to recurrence

    Measured: From date of Complete Response (CR) to first recurrence of HCC, up to 3 years

Secondary outcomes (3)

  1. Disease-free Survival

    Measured: From date of CR to first recurrence of HCC or death, due to any cause, up to 3 years

  2. Disease-free Specific Survival

    Measured: From date of CR to first recurrence of HCC or death, due to HCC, up to 3 years

  3. Overall Survival

    Measured: From diagnosis to date of death due to any cause, up to 3 years

Timeline

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

  1. First posted30 Aug 2017
  2. Study start16 May 2016
  3. Primary completion31 Mar 2021
  4. Study completion31 Mar 2021

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03267641
Sponsor's protocol ID
AHCC07
Acronym
PLANET
Status last verified
Jun 2021
First submitted
28 Aug 2017
Last updated
9 Jun 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Chen J, Kaya NA, Zhang Y, Kendarsari RI, Sekar K, Lee Chong S, Seshachalam VP, Ling WH, Jin Phua CZ, Lai H, Yang H, Lu B, Lim JQ, Ma S, Chew SC, Chua KP, Santiago Alvarez JJ, Wu L, Ooi L, Yaw-Fui Chung A, Cheow PC, Kam JH, Wei-Chieh Kow A, Ganpathi IS, Bunchaliew C, Thammasiri J, Koh PS, Bee-Lan Ong D, Lim J, de Villa VH, Dela Cruz RD, Loh TJ, Wan WK, Leow WQ, Yang Y, Liu J, Skanderup AJ, Pang YH, Ting Soon GS, Madhavan K, Kiat-Hon Lim T, Bonney G, Goh BKP, Chew V, Dan YY, Toh HC, Sik-Yin Foo R, Tam WL, Zhai W, Kah-Hoe Chow P. A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory. J Hepatol. 2024 Oct;81(4):667-678. doi: 10.1016/j.jhep.2024.05.017. Epub 2024 May 21.

    PubMed 38782118

  • Nguyen PHD, Ma S, Phua CZJ, Kaya NA, Lai HLH, Lim CJ, Lim JQ, Wasser M, Lai L, Tam WL, Lim TKH, Wan WK, Loh T, Leow WQ, Pang YH, Chan CY, Lee SY, Cheow PC, Toh HC, Ginhoux F, Iyer S, Kow AWC, Young Dan Y, Chung A, Bonney GK, Goh BKP, Albani S, Chow PKH, Zhai W, Chew V. Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma. Nat Commun. 2021 Jan 11;12(1):227. doi: 10.1038/s41467-020-20171-7.

    PubMed 33431814

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 6 sites in 4 countries.

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 22 inclusion and 13 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 9 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Singapore, Malaysia, Philippines, Thailand. 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.

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?

Time to recurrence (time frame: From date of Complete Response (CR) to first recurrence of HCC, up to 3 years). 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 NCT03267641, 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 9 Jun 2021.

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