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A Study to Assess a PI3Kδ Inhibitor (IOA-244) in Patients With Metastatic Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04328844
Recruitment Status : Recruiting
First Posted : March 31, 2020
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
iOnctura

Brief Summary:

The objective of study IOA-244-101 is to determine whether IOA-244 is safe and tolerable in cancer patients (Part A). In addition, the study will assess whether IOA-244 can increase the anti-tumour immune response in patients both as monotherapy and in combination with pemetrexed/cisplatin (Part B).

Participants will receive IOA-244 for a period of 6 months. After treatment completion, participants will continue in the study for a follow-up period of 6 months.


Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: IOA-244 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Sequential Assignment
Intervention Model Description: This is a two-part FIH dose study, where Part A is a dose-escalation group treatment study with IOA-244 and Part B is a parallel cohort study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-in-Human Dose Study of IOA-244 Alone and in Combination With Pemetrexed/Cisplatin in Patients With Advanced or Metastatic Cancers
Actual Study Start Date : February 25, 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : April 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arm Intervention/treatment
Experimental: Single arm with IOA-244 Drug: IOA-244
IOA-244 will be administered orally once daily (QD)




Primary Outcome Measures :
  1. Numbers of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: From time of first drug administration to first documented progression, toxicity or death from any cause whichever occurs first, assessed at week 30 ]
    Adverse Events will be assessed by nondirective questioning of the participants during the screening process, at each visit during the study and during the safety follow up period


Secondary Outcome Measures :
  1. Cmax [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Peak Plasma Concentration

  2. Cmin [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Minimum observed plasma concentration

  3. t½ [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Terminal elimination half-life

  4. tmax [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Time of the maximum observed plasma concentration

  5. AUC0-t [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

  6. AUC0-∞ [ Time Frame: At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Area under the plasma concentration-time curve from time zero extrapolated to infinity

  7. Pharmacodynamic activity of IOA-244 by determining changes in Lymphocytes counts [ Time Frame: At Cycle 1 Day 1, Day 2, Day 15 (pre-dose), From Cycle 2 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days ]
    Lymphocytes Immunophenotyping in peripheral blood

  8. Pharmacodynamic activity of IOA-244 by determining changes in LDH [ Time Frame: At Screening (D-28 to D-1), Cycle 1 Day 1, Day 8, Day 15, Day 22 (pre-dose). Each cycle is 28 days ]
    Levels of Lactate Dehydrogenase (LDH)

  9. Pharmacodynamic activity of IOA-244 by evaluating levels of Mesothelin [ Time Frame: At Cycle 1, Day 1 and Day 15 (pre-dose) , From Cycle 2 to Cycle 6, Day 1 (pre-dose). Each cycle is 28 days ]
    Levels of Mesothelin (Mesothelioma participants only)

  10. Objective Response Rate (ORR) [ Time Frame: Up to 28 weeks ]
    Percentage of participants with a Complete Response (CR) or Partial Response (PR) RECIST 1.1, or for participants with Mesothelioma, modified RECIST

  11. Duration of response (DOR) [ Time Frame: From date of the first documented evidence of CR or PR until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 54 weeks ]
    DOR among patients who achieve objective response as determined by radiographic disease assessment

  12. Progression Free Survival (PFS) [ Time Frame: From date of the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 104 weeks ]
  13. Overall Survival (OS) [ Time Frame: From date of the first dose of study treatment until the date of death from any cause, assessed up to 150 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥18 years of age inclusive, at the time of signing the informed consent
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  3. Patients with histologically or cytologically confirmed advanced or metastatic melanoma (histologically confirmed, unresectable Stage III or IV melanoma), mesothelioma or ocular/uveal melanoma

Exclusion Criteria:

  1. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications
  2. Have prior significant medical history and adverse events (AEs):

    1. History of a prior Grade 3 or 4 immune-related AE (irAE) or any grade ocular irAE from prior immunotherapy
    2. Active autoimmune process (e.g., rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
    3. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not required steroids for at least 7 days before study treatment
    4. History or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval > 480 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is > 480 milliseconds, the patient may enrol if the average QTc for the 3 ECGs is < 480 milliseconds. For patients with an intraventricular conduction delay (QRS interval > 120 msec), the JTc interval may be used in place of the QTc with Sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Patients with left bundle branch block are excluded Note: QTc prolongation due to pacemaker may enrol if the JT is normal or with Medical Monitor approval
    5. Evidence of interstitial lung disease or active, non-infectious pneumonitis
    6. Active infection requiring systemic therapy
    7. Known additional malignancy that is progressing or requires active treatment Patients with active malignancy requiring concurrent intervention or previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period.
    8. Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy
  3. Treatment with anticancer medications, investigational drugs, surgery and/or radiation within the following interval before the first administration of study drug:

    1. < 14 days for chemotherapy, targeted small-molecule therapy, surgical resection of lesions or radiation therapy (prior palliative radiotherapy must have been completed at least 14 days prior to study drug administration). Patients must also not require corticosteroids and must not have had pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non-CNS disease with Sponsor approval Note: The use of denosumab is permitted
    2. < 14 days for a prior PD-1 pathway-targeted agent
    3. < 28 days for prior monoclonal antibody used for anticancer therapy with the exception of PD-1 pathway-targeted agents
    4. < 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices. For investigational agents with long half-lives (e.g., > 5 days), enrolment before the fifth half-life requires Medical Monitor approval

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04328844


Contacts
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Contact: Michael Lahn, MD +0041795066366 m.lahn@ionctura.com

Locations
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Italy
Medical Oncology and Immunotherapy Unit, University Hospital of Siena Recruiting
Siena, Italy, 53100
Contact: Michele Maio, MD       mmaio@cro.it   
Principal Investigator: Michele Maio, MD         
United Kingdom
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Jeff Evans, MD       Jeff.Evans@ggc.scot.nhs.uk   
Principal Investigator: Jeff Evans, MD         
Sponsors and Collaborators
iOnctura
Investigators
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Study Director: Michael Lahn iOnctura
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Responsible Party: iOnctura
ClinicalTrials.gov Identifier: NCT04328844    
Other Study ID Numbers: IOA-244-101
2019-000686-20 ( EudraCT Number )
First Posted: March 31, 2020    Key Record Dates
Last Update Posted: April 3, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by iOnctura:
Mesothelioma
Melanoma
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes