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Pancreatic CancerPhase 1/2MIKE-1NCT05064618

Investigator-initiated Clinical Trial of MIKE-1

A Phase 1/2 study testing Am80, Gemcitabine and nab-Paclitaxel in people with Pancreatic Cancer, run by Nagoya University at 2 sites in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

To evaluate the safety and tolerability of Am80（Generic name: Tamibarotene, Development code: MIKE-1） in combination with gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with unresectable pancreatic cancer and to determine the recommended dose. Efficacy will also be exploratively investigated. Read more about this study

Who is it for?
Ages 20 to 79 years
Conditions the study is for
Pancreatic Cancer
What is being tested?
Am80, Gemcitabine and nab-Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
2 sitesJapan
Study dates
23 Aug 2021to 30 Apr 2025
Phase
Phase 1/2
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 20 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who meet all of the following criteria will be eligible for this study. Besides, CTCAE v5.0 will be used to determine the grade of adverse events in this study.
  • Patients with unresectable pancreatic cancer who are histologically or cytologically diagnosed as adenocarcinoma based on the 7th edition of the Pancreatic Cancer Treatment Protocol and meet the following criteria.
  • Patients who have not received any anticancer therapy (radiation therapy, chemotherapy, immunotherapy, surgery, or investigational therapy) for this disease.
  • Patients who are between 20 and 79 years of age at the time of consent.
  • Patients with at least one measurable lesion based on RECIST ver 1.1 in the primary pancreatic lesion confirmed by contrast-enhanced CT at the screening.
  • Patients who are expected to survive for at least 12 weeks after the start of treatment.
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  • Patients who can understand the contents of this study and can give written consent.
  • Patients with ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
  • Patients who meet the following criteria in blood tests within 7 days before enrollment and whose organ functions are preserved (if blood transfusion is used, tests must be performed at intervals of at least 2 weeks afterward)
  • Total bilirubin ≤ upper limit of institutional standard (ULN) x 1.5 (less than or equal to 3.0 mg/dL for patients undergoing ERBD or PTBD)
  • AST (GOT) and ALT (GPT) ≦ ULN × 3 (In the case of abnormal liver function due to malignancy, ≤ ULN × 5)
  • Creatinine ≤ 1.5 mg/dL or
  • Creatinine clearance ≥ 60ml/min If creatinine clearance is not measured, the estimated value should be used.
  • White blood cell count ≥ 3,500/mm3, ≤ 12,000/mm3
  • Neutrophils ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9.0g/dL
  • Prothrombin activity level ≥ 70%
  • Outpatients who can go to the hospital.
  • Patients who can swallow or continue to take oral medications.
  • For women of childbearing potential, patients who can use contraception for at least 30 days before the start of study treatment, during the study period, and for at least 2 years after the end of treatment.
  • Patients who can undergo biopsy from pancreatic cancer ①within 28 days before the start of the study treatment and ② 8 weeks after the start of the study treatment (Day 57: acceptable range: ±7 days)

Who cannot join

  • Patients with any of the following complications Patients with poorly controlled heart disease (congestive heart failure, myocardial infarction, or unstable angina within 1 year before enrollment, arrhythmia requiring treatment, etc.) Poorly controlled diabetes or hypertension Active autoimmune disease requiring systemic administration of steroids or immunosuppression therapy Interstitial pneumonia or pulmonary fibrosis (patients with current grade 2 or higher)
  • Patients who have received other clinical trial drugs or products (excluding existing chemotherapeutic agents and placebo drugs) within 4 weeks before enrolment.
  • Patients with confirmed brain metastasis (confirmed by head CT or MRI if the patient has symptoms of brain metastasis)
  • Patients with ascites or pleural effusion requiring drainage.
  • Patients who fall under any of the following HBs antigen positive HCV antibody positive and HCV-RNA positive HIV antibody positive
  • Patients with Grade 2 or higher peripheral sensory or motor neuropathy
Show all 18Show fewer
  • Patients with multiple cancers (multiple cancers are defined as simultaneous multiple cancers and metachronous multiple cancers with disease-free survival of 5 years or less. lesions equivalent to carcinoma in situ or intramucosal carcinoma that are considered curable by local treatment are not included in multiple cancers)
  • Patients who have undergone surgery (excluding diagnostic biopsy and review laparoscopy) within 4 weeks before enrollment.
  • Patients with bleeding disorders or coagulation disorders that preclude the safe biopsy under EUS (e.g., significant intratumoral bleeding, coagulation disorders, history of bleeding disorders, or complications).
  • Patients with a history of allergy to the trial drug, combination chemotherapy, its additives, or vitamin A products.
  • Patients requiring anticoagulant medication.
  • Patients with cerebral infarction, pulmonary infarction, other arterial or venous thrombosis or its sequelae with clinical symptoms.
  • Patients with gastrointestinal disorders that may affect the absorption of the investigational drug.
  • Female patients who are pregnant or breastfeeding (unless breastfeeding is discontinued and not resumed).
  • Male patients whose sex partner is a woman who wishes to become pregnant.
  • Patients with vitamin A overload.
  • Patients receiving vitamin A preparations or regularly using vitamin A-containing supplements (patients can be enrolled if the administration is discontinued at the time of obtaining consent).
  • Other patients deemed inappropriate by the investigator or sub-investigator.

Trial locations and contacts

2 sites in 1 country.

Yasuyuki Mizutani contact

+81-52-741-2111

y-mizu@med.nagoya-u.ac.jp

Toshihisa Tsuruta contact

+81-52-741-2111

ttsuruta@med.nagoya-u.ac.jp

Japan2 sites, 2 recruiting

  • Nagoya University Hospital

    Nagoya, Aich, 466-8560

    Yasuyuki Mizutani, +81-52-741-2111, y-mizu@med.nagoya-u.ac.jp

    Tsuruta Toshihisa, +81-52-741-2111, ttsuruta@med.nagoya-u.ac.jp

    Recruiting

  • The University of Tokyo Hospital

    Tokyo

    Ｋensaku Ｎoguchi, +81 03 3815 5411, kensaku.noguchi.23@gmail.com

    Not yet recruiting

Other trials in Japan

About this study

Official title: Phase I/II Investigator-initiated Clinical Trial of MIKE-1 With Gemcitabine and Nab-paclitaxel Combination Therapy for Unresectable Pancreatic Cancer

To evaluate the safety and tolerability of Am80（Generic name: Tamibarotene, Development code: MIKE-1） in combination with gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with unresectable pancreatic cancer and to determine the recommended dose. Efficacy will also be exploratively investigated.

Read the detailed description

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment. The most common notion in the CAF research field has been that CAFs promote cancer progression through various mechanisms. Interestingly, however, recent studies have revealed that CAFs are heterogeneous and that CAF subsets that suppress cancer progression (cancer-restraining CAFs [rCAFs]) must exist in addition to well-characterized cancer-promoting CAFs (pCAFs). However, the identity and specific markers of rCAFs have not been reported.

The investigators recently identified Meflin as a specific marker protein of rCAFs in pancreatic and colon cancers. The investigator's studies revealed that rCAFs are similar to a small subset of resident fibroblasts, which is consistent with the famous hypothesis proposed by Micheal Stoker (University of Glasgow) more than 50 years ago, stating that static normal fibroblasts suppress tumor growth. Interestingly, The investigator's lineage tracing experiments showed that Meflin-positive rCAFs differentiate into Meflin-negative pCAFs during cancer progression. These studies revealed that the tumor stroma is comprised of pCAFs and rCAFs, which is analogous to the heterogeneity of tumor-infiltrating immune cells (e.g., protumor regulatory T cells versus antitumor cytotoxic T cells).

The identification of the rCAF marker Meflin enabled the investigators to develop new strategies to convert or reprogram pCAFs to rCAFs. Using a pharmacological approach, The investigators performed a chemical library screen and identified Am80, a synthetic unnatural retinoid, as a reagent that effectively converts Meflin-negative pCAFs to Meflin-positive rCAFs. Am80 administration improved the sensitivity of pancreatic cancer to chemotherapeutics. These data suggested that the conversion of pCAF to rCAFs may represent a new strategy for pancreatic cancer treatment.

The object of this study is to perform an investigator-initiated clinical study to investigate the effect of AM80 on pancreatic cancer with a combination of conventional tumoricidal agents including gemcitabine and nab-paclitaxel.

Being tested
Am80, Gemcitabine, nab-Paclitaxel
Keywords
Am80, Meflin, Cancer-associated fibroblasts, Tamibarotene, ISLR, Cancer-restraining CAFs, Cancer-promoting CAFs, MIKE-1, Vitamin A
Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • Am80Drug

    Also called Tamibarotene, MIKE-1

    medicine taken internally

  • GemcitabineDrug

    Also called GEM

    Administered intravenously at a dose of 1000mg/m2

  • nab-PaclitaxelDrug

    Also called nab-PTX

    Administered intravenously at a dose of 125mg/m2

Study groups in NCT05064618
Study groupRoleWhat they receive
Am80+GEM/nab-PTX (Phase I)Experimental●The dose-limiting toxicity (DLT) assessment period will be set at 4 weeks. After the DLT evaluation period, if no disease progression is observed based on RECIST v1.1, or no unacceptable toxicities are observed in the patient, the investigational drug will be administered orally twice a day after breakfast and dinner for up to 6 courses for each dosage group. However, for the modified dosage level 2 of the Phase I trial, the investigational drug will be administered orally twice a day after breakfast and dinner, starting from the first day (Day 1) of each course, and drug administration will be paused starting from the Day 15 GEM/nab-PTX administration. Furthermore, dose reduction or increase of the investigational drug will not be performed on the same subject. Level 1: 6 mg (3 capsules). Level 2 \& Modified Level 2: 8 mg (4 capsules). Level 0: 4 mg (2 capsules) if DLT seen in >33% of Level 1. ●(Phase I / II study) GEM (1000mg/m2) and nab-PTX (125mg/m2) are given intravenously.
Receives: Drug: Am80; Drug: Gemcitabine; Drug: nab-Paclitaxel
Am80+GEM/nab-PTX (Phase II)ExperimentalThe investigational drug at the clinically recommended dose determined in the Phase I trial will be administered orally twice a day after breakfast and dinner, starting from the first day (Day 1) of each course, and drug administration will be paused starting from the Day 15 GEM/nab-PTX administration. This will continue for up to 6 courses. Furthermore, dose reduction or increase of the investigational drug will not be performed on the same subject.
Receives: Drug: Am80; Drug: Gemcitabine; Drug: nab-Paclitaxel

What is being measured

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

  1. Phase I study; DLT (dose-limiting toxicity)

    The severity of adverse events will be determined by the investigator based on CTCAE v 5.0.

    • Grade 4 hematologic toxicity that persists for more than 7 days
    • Grade 3 or higher non-hematologic toxicity that persists for more than 7 days despite symptomatic treatment
    • An adverse event that caused the inability to administer both Day 8 and Day 15 of Cycle 1 of GEM or nab-PTX
    • An adverse event that caused the inability to administer Day 8 of the first cycle of GEM or nab-PTX, resulting in a reduced dose of Day 15

    Measured: The DLT evaluation period is from Day 1, the start date of study drug administration, to Day 28 of Phase I study.

  2. Phase II study; response rate (based on RECIST ver1.1)

    If each subject has measurable disease, tumor shrinkage efficacy determination (CR, PR, SD, PD, NE) will be performed based on RECIST v1.1.

    Measured: through phase II study completion,an average of half year.

Secondary outcomes (10)

  1. AE（Adverse events）

    Adverse events will be classified and tabulated in MedDRA/J.

    Measured: All of the clinical trial period (up to 6 cycles, 28 days per cycle)

  2. OS（Overall survival）

    The distribution of overall survival will be estimated by the Kaplan-Meier method, the Kaplan-Meier curve will be illustrated, and the median and 95% confidence interval will be calculated.

    Measured: The time from the date of first dose of MIKE-1 until date of death from any cause. The cut-off date is the end of post-observation for all patients.

  3. PFS（Progression-free survival）

    The distribution of progression-free survival will be estimated by the Kaplan-Meier method, the Kaplan-Meier curve will be illustrated, and the median and 95% confidence interval will be calculated.

    Measured: The time from date of first dose of MIKE-1 to date of first documentation of disease progression or death, whichever occurs. The cut-off date is the end of post-observation for all patients.

  4. Area under the blood concentration time curve (AUC)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  5. Peak Plasma Concentration (Cmax)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  6. Elimination half-life (t1/2)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  7. Clearance (CL)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  8. Mean residence time (MRT)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  9. Volume of distribution (Vds)

    Calculate summary statistics

    Measured: 1, 2, 4, 8, 10, and 24 hours after first dosing in phase I.

  10. Response rate （Phase I）

    Based on RECIST ver1.1

    Measured: All of the clinical trial period (up to 6 cycles, 28 days per cycle)

Timeline

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

  1. First posted1 Oct 2021
  2. Study start23 Aug 2021
  3. Primary completion30 Apr 2025 (estimated)
  4. Study completion30 Apr 2025 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Groups of participants are assigned to receive interventions based on prior milestones being reached in the study, such as in some dose escalation and adaptive design studies.
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05064618
Sponsor's protocol ID
CAMCR-016
Other IDs
jRCT2041210056
Acronym
MIKE-1
Status last verified
Apr 2024
First submitted
18 Aug 2021
Last updated
4 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MW, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M. Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis. Cancer Res. 2019 Oct 15;79(20):5367-5381. doi: 10.1158/0008-5472.CAN-19-0454. Epub 2019 Aug 22.

    PubMed 31439548

  • Kobayashi H, Gieniec KA, Wright JA, Wang T, Asai N, Mizutani Y, Lida T, Ando R, Suzuki N, Lannagan TRM, Ng JQ, Hara A, Shiraki Y, Mii S, Ichinose M, Vrbanac L, Lawrence MJ, Sammour T, Uehara K, Davies G, Lisowski L, Alexander IE, Hayakawa Y, Butler LM, Zannettino ACW, Din MO, Hasty J, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Wang TC, Enomoto A, Takahashi M, Worthley DL, Woods SL. The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. Gastroenterology. 2021 Mar;160(4):1224-1239.e30. doi: 10.1053/j.gastro.2020.11.011. Epub 2020 Nov 14.

    PubMed 33197448

  • Stoker MG, Shearer M, O'Neill C. Growth inhibition of polyoma-transformed cells by contact with static normal fibroblasts. J Cell Sci. 1966 Sep;1(3):297-310. doi: 10.1242/jcs.1.3.297. No abstract available.

    PubMed 4291022

  • Iida T, Mizutani Y, Esaki N, Ponik SM, Burkel BM, Weng L, Kuwata K, Masamune A, Ishihara S, Haga H, Kataoka K, Mii S, Shiraki Y, Ishikawa T, Ohno E, Kawashima H, Hirooka Y, Fujishiro M, Takahashi M, Enomoto A. Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics. Oncogene. 2022 May;41(19):2764-2777. doi: 10.1038/s41388-022-02288-9. Epub 2022 Apr 13.

    PubMed 35414659

  • Mizutani Y, Iida T, Ohno E, Ishikawa T, Kinoshita F, Kuwatsuka Y, Imai M, Shimizu S, Tsuruta T, Enomoto A, Kawashima H, Fujishiro M. Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma. BMC Cancer. 2022 Feb 24;22(1):205. doi: 10.1186/s12885-022-09272-2.

    PubMed 35209871

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Am80, Gemcitabine and nab-Paclitaxel in people with Pancreatic Cancer, run by Nagoya University at 2 sites in Japan.

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 18 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: status not confirmed, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Japan. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Yasuyuki Mizutani (+81-52-741-2111, y-mizu@med.nagoya-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I study; DLT (dose-limiting toxicity) (time frame: The DLT evaluation period is from Day 1, the start date of study drug administration, to Day 28 of Phase I study.). 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 NCT05064618, which also lists 5 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 4 Apr 2024.

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