Advanced or Metastatic Solid TumorsPhase 1NCT03616574

First-in-human Study of CA102N Monotherapy and CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors

A Phase 1 study testing CA102N and LONSURF in people with Advanced or Metastatic Solid Tumors and Advanced or Metastatic Colorectal Cancer (mCRC), run by Holy Stone Healthcare Co., Ltd at 3 sites in United States.

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

Study HS-CA102N-101 is a phase 1, two part (dose escalation, dose expansion), multicenter, non-randomized, open-label, multiple dose, first-in-human study of CA102N monotherapy and of CA102N combined with trifluridine/tipiracil (LONSURF) in subjects with advanced solid tumors. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced or Metastatic Solid Tumors, Advanced or Metastatic Colorectal Cancer (mCRC)
What is being tested?: CA102N and LONSURF
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 3 sitesUnited States
Study dates: 9 Apr 2019to 1 Mar 2022
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

Subjects enrolled in Part 1 must have histologically documented locally advanced or metastatic solid tumor for which there is no effective therapy available.
Subjects enrolled in Part 2 must have histologically documented locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Age ≥18 years (US) or ≥20 years (Taiwan).
ECOG performance status 0-1.
Measurable or non-measurable disease based on RECIST version 1.1. Subjects enrolled in Part 2 must have at least one measurable lesion.
Adequate organ function within 14 days before 1st dose of study drug, defined as:

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Platelet count ≥ 100,000/mm3.
Hemoglobin ≥ 9.0 g/dL.
Absolute neutrophil count ≥ 1500/mm3 (without hematopoietic growth factor support).
Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation.
Aspartate aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
Alanine aminotransferase: (i) ≤3 x ULN in subjects without liver metastasis or ≤5 x ULN in subjects with liver metastasis in CA102N monotherapy treatment group; (ii) ≤3 x ULN in subjects who will be treated with CA102N combined with trifluridine/tipiracil (LONSURF).
Total bilirubin ≤1.5 x ULN (unless documented Gilbert's Syndrome).
Has had an adequate treatment washout period prior to 1st dose of study drug defined as:
No major surgery within the past 4 weeks.
No extended field radiation therapy within the prior 4 weeks.
No anticancer therapy or bevacizumab within the prior 3 weeks.
No investigational agent received within prior 4 weeks (or 5 times the half-life of the investigational agent, whichever is shorter).
No aspirin or NSAIDs for at least 72 hours before 1st dose of study drug.
No herbal supplements taken as anticancer agents within the prior 7 days.
Able to provide written informed consent.
Life expectancy of ≥ 3 months.
Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective means of contraception from study entry through at least 6 months after the last dose of CA102N. Women of childbearing potential are those women who have not been permanently sterilized or are not postmenopausal.

Who cannot join

For Part 2, active malignancies other than colorectal cancer.
History of hypersensitivity or hepatotoxic reaction to nimesulide or to any excipient.
Requiring therapeutic doses of anticoagulants.
History or presence of a bleeding tendency or disorder.
History of gastrointestinal bleed or perforation related to previous NSAID therapy.
Presence or history of recurrent peptic ulcer or hemorrhage.

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History of cerebrovascular or other active bleeding.
Myocardial infarction within the last 12 months, severe or unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) Class III or IV.
History of a serious cardiac arrhythmia requiring treatment.
Corrected QT prolongation using Fridericia formula (QTcF), of > 450 msec for males or > 470 msec for females based on a triplicate 12-lead ECG.
Clinically significant lung disease (eg, interstitial pneumonia, interstitial lung disease, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) requiring continuous systemic corticosteroid treatment for 6 months before registration or who are suspected to have such diseases by imaging at Screening.
Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks.
Active autoimmune disease that has required systemic treatment in past 2 years.
History of allogeneic transplantation requiring immunosuppressive therapy.
Known positive test for hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV).
Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
Pregnant or breast feeding.
Unresolved toxicity of greater than or equal to NCI-CTCAE (version 5.0) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).
Concomitant medical condition that would increase the risk of toxicity, in the opinion of the Investigator.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
MD Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase 1,Two-part (Dose Escalation, Dose Expansion), Multicenter,Non-randomized,Open-label, Multiple Dose, First-in-human Study of CA102N Monotherapy and of CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors

CA102N will be evaluated in subjects with locally advanced or metastatic solid tumours for which no effective therapy is available in Part 1 (dose escalation) and in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer (mCRC) after prior oxaliplatin and irinotecan-based chemotherapy in Part 2 (dose expansion).

Read the detailed description

Part 1 (dose escalation) will determine the safety and tolerability of three dose levels of CA102N as monotherapy and the safety, tolerability and preliminary recommended phase 2 dose (RP2D) of CA102N in combination with trifluridine/tipiracil (LONSURF) in patients with locally advanced or metastatic solid tumors.

Part 2 (dose expansion) will further investigate the safety and tolerability of the combination of CA102N and trifluridine/tipiracil (LONSURF) at the preliminary RP2D in patients with locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and if RAS wild-type metastatic colorectal cancer, an anti-epidermal growth factor receptor (EGFR) therapy..

Preliminary efficacy will be evaluated in Parts 1 and 2 of the study as an exploratory endpoint.

Conditions: Advanced or Metastatic Solid Tumors, Advanced or Metastatic Colorectal Cancer (mCRC)
Being tested: CA102N, LONSURF
Medical subject headings: Colorectal Neoplasms

What participants receive

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

CA102NDrug
Also called Nim-HA Conjugate
CA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim).
LONSURFDrug
Also called Trifluridine/Tipiracil
LONSURF is a cytotoxic combination treatment of 2 new drugs: trifluridine, a thymidine-based nucleoside analog, and tipiracil, an inhibitor of thymidine phosphorylase.

Study groups in NCT03616574
Study group	Role	What they receive
Dose Escalation - CA102N Monotherapy	Experimental	0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 of a 28-day cycle Receives: Drug: CA102N
Dose Escalation - CA102N plus LONSURF	Experimental	0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle Receives: Drug: CA102N; Drug: LONSURF
Dose Expansion - CA102N plus LONSURF	Experimental	The preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle Receives: Drug: CA102N; Drug: LONSURF

What is being measured

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

Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0
The primary endpoint for the study is the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF) as determined according to the NCI-CTCAE version 5.0.
Measured: The safety measures will be assessed and recorded throughout the trial until 30 days following treatment termination (an average of 1 year).

Secondary outcomes (1)

Serum concentration of CA102N
The secondary endpoint of the study is to measure serum concentration of CA102N (ng/mL).
Measured: Serum sampling timepoints: predose, 0.5,1, 2, 4, 8, 12, 24, 48, and 72 hours postdose CA102N on Days 1 and 15 at Cycle 1 (each cycle is 28 days).

Timeline

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

9 Apr 20191 Mar 2022

First posted6 Aug 2018
Study start9 Apr 2019
Primary completion8 Feb 2022
Study completion1 Mar 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Sequential
Model description: Part 1 (dose escalation) of the study will use a conventional 3+3 design (3 subjects per dose cohort, with the potential to add an additional 3 subjects if dose limiting toxicity \[DLT\] is observed at the same dose level at which the toxicity occurred). Enrollment will occur in 2 groups, CA102N monotherapy (Group A) and CA102N combination therapy (Group B). Subjects will be enrolled in Group A first. Once enrollment in Group A has been completed, subsequent subjects will be enrolled in Group B. In Part 2 of the study, the safety and tolerability of the preliminary RP2D of CA102N combined with trifluridine/tipiracil (LONSURF) will be further evaluated in up to 12 additional subjects with relapsed or refractory locally advanced or metastatic colorectal cancer who have previously received oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03616574
Sponsor's protocol ID: HS-CA102N-101
Status last verified: Mar 2022
First submitted: 26 Jun 2018
Last updated: 21 Sep 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Jian YS, Chen CW, Lin CA, Yu HP, Lin HY, Liao MY, Wu SH, Lin YF, Lai PS. Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo. Int J Nanomedicine. 2017 Mar 27;12:2315-2333. doi: 10.2147/IJN.S120847. eCollection 2017.
PubMed 28392690
Pant S, Dragovich T, Lieu C, Jimeno A, Kundranda M, Menter D, Tchaparian E, Chen YC, Kopetz S. Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2023 Feb;41(1):25-34. doi: 10.1007/s10637-022-01308-5. Epub 2022 Nov 4.
PubMed 36331676

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1,Two-part (Dose Escalation, Dose Expansion), Multicenter,Non-randomized,Open-label, Multiple Dose, First-in-human Study of CA102N Monotherapy and of CA102N Combined With Trifluridine/Tipiracil (LONSURF) in Subjects With Advanced Solid Tumors
ClinicalTrials.gov ID: NCT03616574
Acronym / sponsor ID: HS-CA102N-101
Conditions: Advanced or Metastatic Solid Tumors, Advanced or Metastatic Colorectal Cancer (mCRC)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Holy Stone Healthcare Co., LtdIndustry (pharma, biotech, devices)
Study start: 9 Apr 2019 (actual)
Primary completion: 8 Feb 2022 (actual)
Study completion: 1 Mar 2022 (actual)
First posted: 6 Aug 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Preliminary efficacy will be evaluated in Parts 1 and 2 of the study as an exploratory endpoint.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3
Model description: Part 1 (dose escalation) of the study will use a conventional 3+3 design (3 subjects per dose cohort, with the potential to add an additional 3 subjects if dose limiting toxicity [DLT] is observed at the same dose level at which the toxicity occurred). Enrollment will occur in 2 groups, CA102N monotherapy (Group A) and CA102N combination therapy (Group B). Subjects will be enrolled in Group A first. Once enrollment in Group A has been completed, subsequent subjects will be enrolled in Group B. In Part 2 of the study, the safety and tolerability of the preliminary RP2D of CA102N combined with trifluridine/tipiracil (LONSURF) will be further evaluated in up to 12 additional subjects with relapsed or refractory locally advanced or metastatic colorectal cancer who have previously received oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Arm	Type	Receives
Dose Escalation - CA102N Monotherapy	Experimental	Drug: CA102N0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 of a 28-day cycle
Dose Escalation - CA102N plus LONSURF	Experimental	Drug: CA102N, Drug: LONSURF0.36, 0.54, and 0.72 mg/kg of nimesulide equivalents of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle
Dose Expansion - CA102N plus LONSURF	Experimental	Drug: CA102N, Drug: LONSURFThe preliminary RP2D of CA102N on Days 1 and 15 in combination with 35 mg/m2/dose of LONSURF orally twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (23 listed)

Subjects enrolled in Part 1 must have histologically documented locally advanced or metastatic solid tumor for which there is no effective therapy available.
Subjects enrolled in Part 2 must have histologically documented locally advanced or metastatic colorectal cancer that has relapsed after or is refractory to oxaliplatin and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.
Age ≥18 years (US) or ≥20 years (Taiwan).
ECOG performance status 0-1.
Measurable or non-measurable disease based on RECIST version 1.1. Subjects enrolled in Part 2 must have at least one measurable lesion.

Key exclusion criteria (19 listed)

For Part 2, active malignancies other than colorectal cancer.
History of hypersensitivity or hepatotoxic reaction to nimesulide or to any excipient.
Requiring therapeutic doses of anticoagulants.
History or presence of a bleeding tendency or disorder.
History of gastrointestinal bleed or perforation related to previous NSAID therapy.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CA102NAlso: Nim-HA ConjugateCA102N is a covalently bound conjugate of the biological polymer sodium hyaluronate (NaHA) and nimesulide (Nim).	Drug	Dose Escalation - CA102N Monotherapy, Dose Escalation - CA102N plus LONSURF, Dose Expansion - CA102N plus LONSURF
LONSURFAlso: Trifluridine/TipiracilLONSURF is a cytotoxic combination treatment of 2 new drugs: trifluridine, a thymidine-based nucleoside analog, and tipiracil, an inhibitor of thymidine phosphorylase.	Drug	Dose Escalation - CA102N plus LONSURF, Dose Expansion - CA102N plus LONSURF

Primary outcome

Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Time frame: The safety measures will be assessed and recorded throughout the trial until 30 days following treatment termination (an average of 1 year).
The primary endpoint for the study is the safety and tolerability of CA102N monotherapy and CA102N combined with trifluridine/tipiracil (LONSURF) as determined according to the NCI-CTCAE version 5.0.

1 secondary outcome

Serum concentration of CA102N
Time frame: Serum sampling timepoints: predose, 0.5,1, 2, 4, 8, 12, 24, 48, and 72 hours postdose CA102N on Days 1 and 15 at Cycle 1 (each cycle is 28 days).

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2022.
Background: PubMed 28392690Jian YS, Chen CW, Lin CA, Yu HP, Lin HY, Liao MY, Wu SH, Lin YF, Lai PS. Hyaluronic acid-nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo. Int J Nanomedicine. 2017 Mar 27;12:2315-2333. doi: 10.2147/IJN.S120847. eCollection 2017.
Derived from this study: PubMed 36331676Pant S, Dragovich T, Lieu C, Jimeno A, Kundranda M, Menter D, Tchaparian E, Chen YC, Kopetz S. Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2023 Feb;41(1):25-34. doi: 10.1007/s10637-022-01308-5. Epub 2022 Nov 4.
Individual participant dataSharing planned: No

Related trials for Advanced or Metastatic Solid Tumors

RecruitingEarly Phase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shubham Pant, MD principal investigator

M.D. Anderson Cancer Center

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 23 inclusion and 19 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 21 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. 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?

Number of subjects with treatment-related adverse events as assessed by NCI-CTCAE v5.0 (time frame: The safety measures will be assessed and recorded throughout the trial until 30 days following treatment termination (an average of 1 year).). 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 NCT03616574, 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 21 Sep 2022.