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Ovarian TumorsPhase 1NCT04711161

First-in-Human Evaluation of GRN-300 in Subjects With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.

A Phase 1 study testing GRN-300 and Paclitaxel in people with Ovarian Tumors, run by Green3Bio, Inc. at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

The study consists of two parts based on the administration of single-agent GRN-300 or in combination with paclitaxel. Part 1 (Phase IA) will test the tolerability of continuous twice a day dosing of oral GRN-300, a salt-inducible kinase inhibitor, with each cycle consisting of 28 days of treatment. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ovarian Tumors
What is being tested?
GRN-300 and Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
1 siteUnited States
Study dates
21 Dec 2020to Mar 2025
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

  • Age ≥ 18 years.
  • Part 1 dose-escalation cohorts: Diagnosis of persistent or recurrent, locally non-resectable or metastatic ovarian, primary peritoneal or fallopian tube epithelial cancer, or advanced solid tumors of any other histology who have progressed on standard therapy and for whom no further effective therapy is available
  • Part 1 dose-expansion cohort / Part 2 dose-escalation cohorts / Part 2 dose-expansion cohort: Diagnosis of persistent or recurrent, locally non-resectable or metastatic ovarian, primary peritoneal or fallopian tube epithelial cancer who have progressed on standard therapy and for whom no further effective therapy is available. Patients with advanced solid tumors of any other histology will not be eligible to be enrolled in these cohorts.
  • Part 2 dose-escalation cohorts / Part 2 dose-expansion cohort: paclitaxel treatment for the tumor should be indicated
  • Histologic or cytologic confirmation of the original tumor by Pathology assessment is required.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension, as defined by RECIST 1.1.
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  • Prior therapy: Patients must have received at least one prior second-line treatment for persistent, recurrent, locally non-resectable or metastatic disease but may have received any number of prior treatments.
  • Any unresolved toxicities from prior therapy should be no greater than NCI-CTCAE v5.0 Grade 1 at screening.
  • Patients who are expected to survive a minimum of three months after the first administration of the study drug.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1.
  • Adequate bone marrow, liver and renal function.

Who cannot join

  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug.
  • Patients with known hypersensitivity to paclitaxel excluded from Part 2 paclitaxel combination only).
  • Use of any cytotoxic chemotherapy or investigational drugs, biologics, or devices within 21 days prior to study enrollment.
  • Women who are pregnant or breastfeeding.
  • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
  • Known CNS metastases or leptomeningeal disease.
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  • Gastrointestinal dysfunction that may affect oral drug absorption (e.g., intermittent or chronic bowel obstruction, short gut, etc.).
  • Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within six months of start of study treatment.
  • Other medical co-morbidities that in the investigator's judgment would increase the risks of participation
  • QTc >480 msec be excluded from the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Ph 1/1B Evaluation of the Safety, Pharmacokinetics and Efficacy of GRN-300, a Salt-inducible Kinase Inhibitor, Alone and in Combination With Paclitaxel, in Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancers.

The study consists of two parts based on the administration of single-agent GRN-300 or in combination with paclitaxel.

Part 1 (Phase IA) will test the tolerability of continuous twice a day dosing of oral GRN-300, a salt-inducible kinase inhibitor, with each cycle consisting of 28 days of treatment. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of dose limiting toxicities (DLTs) or adverse events.

Read more

Part 2 (Phase IB) will test the tolerability of continuous 28-day cycles of GRN-300 in combination with weekly paclitaxel given 3 of 4 weeks per month (x 3).

Overall duration of the study will be approximately 48 months, depending on the rate of enrollment and number of subjects enrolled.

Read the detailed description

Part 1: Phase 1A

Primary objectives:

Determination of the maximum tolerated dose (MTD), if applicable, and recommended Phase II dose (RP2D) of GRN-300 in the study population.

To investigate the safety and tolerability of repeated 28-day cycles of oral GRN-300 therapy in subjects with persistent or recurrent, locally non-resectable or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors.

Secondary objectives:

To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.

To estimate the clinical activity of GRN-300 monotherapy by determining the following:

  • Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)
  • Disease control rate (DCR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a BOR of CR, PR, or stable disease (SD) ≥ 4 months (4 cycles, 28 days each).

Part 2: Phase 1B

Primary objectives:

Determination of the RP2D of GRN-300 in combination with weekly paclitaxel given 3 of 4 weeks per month (x 3) in the study population.

To investigate the safety and tolerability of repeated 28-day cycles of daily oral GRN-300 therapy in combination with weekly paclitaxel x 3 in subjects with persistent or recurrent, locally non-resectable or metastatic, ovarian, fallopian tube, and primary peritoneal cancer, where treatment with paclitaxel is appropriate.

Secondary objectives:

To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.

To estimate the clinical activity of GRN-300 in combination with paclitaxel by determining the following:

  • Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)
  • DCR per investigator assessment using RECIST v.1.1 defined as the percentage of subjects having a BOR of CR, PR, or SD ≥ 4 months (4 cycles, 28 days each).

Exploratory Translational Objectives for Both Study Parts:

  • To estimate progression free survival (PFS) per investigator assessment using RECIST v1.1 for subjects who received continuous GRN-300 and weekly paclitaxel x 3.
  • Evaluate exploratory biomarkers of target engagement and treatment response
Conditions
Ovarian Tumors
Being tested
GRN-300, Paclitaxel
Medical subject headings
Ovarian Neoplasms

What participants receive

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

  • GRN-300Drug

    Also called SIK2/3 Inhibitor

    A salt-inducible kinase (SIK) inhibitor

  • PaclitaxelDrug

    Also called Taxane

    Microtubule inhibitor

Study groups in NCT04711161
Study groupRoleWhat they receive
Part 1 (Phase 1a): Single Arm, Open Label (GRN-300 single-agent)ExperimentalPart 1 of the study will determine the safety of continuous twice a day oral dosing of GRN-300, with each cycle consisting of 28 days of treatment. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of side effects and DLTs. The maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of GRN-300 as a single agent will be determined. The overall duration of Part 1 will be approximately 24-36 months, depending on the rate of enrollment and the number of subjects enrolled.
Receives: Drug: GRN-300
Part 2 (Phase 1b): Single Arm, Open Label (GRN-300 plus paclitaxel)ExperimentalThe study will determine the safety of continuous twice a day oral dosing of GRN-300, with each cycle consisting of 28 days of treatment, in combination with intravenously administered paclitaxel weekly x 3 during each 28-day cycle. The number of administered cycles will depend on the tolerability of each dose level and the severity and occurrence of side effects and DLTs. The maximal tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of GRN-300 in combination with paclitaxel will be determined. The overall duration of Part 2 will be approximately 12-18 months, depending on the rate of enrollment and the number of subjects enrolled. Part 2 will commence following determination of the MTD and RP2D of single-agent GRN-300 in Part 1. Overall duration of the study will be approximately 36-48 months, depending on the rate of enrollment and number of subjects enrolled.
Receives: Drug: GRN-300; Drug: Paclitaxel

What is being measured

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

  1. Part 1 (Phase 1A) - Determination of the MTD and the RP2D of GRN-300 single-agent based on evaluation of the DLT in the study population.

    • Determination of the recommended Phase II dose (RP2D) of GRN-300 in the study population.

    Measured: 24 months

  2. Part 1 (Phase 1A) - Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

    • To investigate the safety of repeated 28-day cycles of daily oral GRN-300 therapy in subjects with recurrent or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors, based on the number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

    Measured: 24 months

  3. Part 2 (Phase 1B) - Determination of the MTD and the RP2D of GRN-300 with paclitaxel based on evaluation of the DLT in the study population

    • Determination of the recommended Phase II dose (RP2D) of GRN-300 in combination with weekly paclitaxel in the study population.

    Measured: 24 months

  4. Part 2 (Phase 1B) - Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

    • To investigate the safety of repeated 28-day cycles of daily oral GRN-300 therapy in combination with weekly paclitaxel x 3 in subjects with recurrent or metastatic ovarian, fallopian tube, and primary peritoneal cancer or other advanced solid tumors, based on the number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

    Measured: 24 months

Secondary outcomes (18)

  1. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (Cmax).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Maximum plasma concentration (Cmax)

    Measured: 24 months

  2. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (tmax).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Time to Cmax (tmax)

    Measured: 24 months

  3. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (t1/2).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Terminal half-life (t1/2)

    Measured: 24 months

  4. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (AUC0-t).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-t)

    Measured: 24 months

  5. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (AUC0-Inf).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Area under the plasma concentration-time curve from zero to infinity (AUC0-Inf)

    Measured: 24 months

  6. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (CL/F).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Apparent oral clearance (CL/F)

    Measured: 24 months

  7. Part 1 (Phase 1A) - Determination of GRN-300 monotherapy PK profile (Vz/F).

    • To evaluate the pharmacokinetic (PK) profile of GRN-300 after oral administration of a single dose and at steady state.
    • Apparent volume of distribution during terminal distribution phase (Vz/F)

    Measured: 24 months

  8. Part 1 (Phase 1A) - Estimation of the clinical activity of single agent GRN-300 (ORR)

    • Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)

    Measured: 24 months

  9. Part 1 (Phase 1A) - Estimation of the clinical activity of single agent GRN-300 (DCR)

    • Disease control rate (DCR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a BOR of CR, PR, or stable disease (SD) ≥ 4 months (4 cycles, 28 days each)

    Measured: 24 months

  10. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (Cmax).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Maximum plasma concentration (Cmax)

    Measured: 24 months

  11. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (tmax).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Time to Cmax (tmax)

    Measured: 24 months

  12. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (t1/2).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Terminal half-life (t1/2)

    Measured: 24 months

  13. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (AUC0-t).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Area under the plasma concentration-time curve from zero to the last measurable concentration (AUC0-t)

    Measured: 24 months

  14. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (AUC0-Inf).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Area under the plasma concentration time curve from zero to infinity (AUC0-Inf)

    Measured: 24 months

  15. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (CL/F).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Apparent oral clearance (CL/F)

    Measured: 24 months

  16. Part 2 (Phase 1B) - Determination of GRN-300 plus paclitaxel PK profile (Vz/F).

    • To evaluate the PK profile of GRN-300 and paclitaxel following administration of a single dose of each and at steady state.
    • Apparent volume of distribution during terminal distribution phase (Vz/F)

    Measured: 24 months

  17. Part 2 (Phase 1B) - Estimation of the clinical activity of GRN-300 plus paclitaxel (ORR).

    • Overall response rate (ORR) per investigator assessment using RECIST v1.1 defined as the percentage of subjects having a best overall response (BOR) of complete response (CR) or partial response (PR)

    Measured: 24 months

  18. Part 2 (Phase 1B) - Estimation of the clinical activity of GRN-300 plus paclitaxel (DCR).

    • DCR per investigator assessment using RECIST v.1.1 defined as the percentage of subjects having a BOR of CR, PR, or SD ≥ 4 months (4 cycles, 28 days each)

    Measured: 24 months

Timeline

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

  1. First posted15 Jan 2021
  2. Study start21 Dec 2020
  3. Primary completionDec 2024 (estimated)
  4. Study completionMar 2025 (estimated)

Why it stopped: Business/Commercial Reasons

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
Non-randomised
Intervention model
Single group
Model description
GRN-300 single-agent and in combination with paclitaxel.
Masking
None (open label)
Enrolment
73 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04711161
Sponsor's protocol ID
GRN300-001
Status last verified
Jan 2024
First submitted
24 Dec 2020
Last updated
23 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GRN-300 and Paclitaxel in people with Ovarian Tumors, run by Green3Bio, Inc. at 1 site in United States.

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 11 inclusion and 10 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: paused, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Results are not available in the source record.

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 (Phase 1A) - Determination of the MTD and the RP2D of GRN-300 single-agent based on evaluation of the DLT in the study population. (time frame: 24 months). The study lists 4 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 NCT04711161.

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 23 Jan 2024.

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