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Study to Evaluate Maximum Tolerated Dose of Oral CB-03-10 With Dose Expansion Phase, in Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03863145
Recruitment Status : Not yet recruiting
First Posted : March 5, 2019
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Cosmo Technologies Ltd

Brief Summary:

Subjects will undergo baseline evaluation and an assessment of extent of disease.

Subjects in Part 1 (Dose Escalation) will receive escalating doses of CB-03-10 based on a modified Fibonacci schema using a standard oncology 3+3 study design to define an MTD and a RP2D. Plasma PK samples will be collected at predetermined timepoints for all subjects.

Subjects in Part 2 (Dose Expansion) of the study will receive CB-03-10 at the RP2D determined in the Part 1 of the study. The indications included in each group will be determined at the completion of Part 1 of the study by Safety Review Committee (SRC).

Subjects will be evaluated weekly initially (for 2 cycles in Part 1 and for 1 cycle in Part 2) and every 2 weeks thereafter. Reassessment of disease will be conducted at Week 8 and every 8 weeks thereafter. Subjects with evidence of response (partial or complete) will be re-evaluated at least 4 weeks later for confirmation.


Condition or disease Intervention/treatment Phase
Advanced Refractory Solid Tumors Subjects Considered Likely to Respond to CB-03-10 Drug: CB-03-10 Early Phase 1

Detailed Description:

Subjects will undergo baseline evaluation and an assessment of extent of disease.

Subjects in Part 1 (Dose Escalation) will receive escalating doses of CB-03-10 based on a modified Fibonacci schema using a standard oncology 3+3 study design to define an MTD and a RP2D. Plasma PK samples will be collected at predetermined timepoints for all subjects.

Subjects in Part 2 (Dose Expansion) of the study will receive CB-03-10 at the RP2D determined in the Part 1 of the study. The indications included in each group will be determined at the completion of Part 1 of the study by Safety Review Committee (SRC).

Subjects will be evaluated weekly initially (for 2 cycles in Part 1 and for 1 cycle in Part 2) and every 2 weeks thereafter. Reassessment of disease will be conducted at Week 8 and every 8 weeks thereafter. Subjects with evidence of response (partial or complete) will be re-evaluated at least 4 weeks later for confirmation.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Part 1 (Dose Escalation): Subjects with advanced refractory solid tumors Part 2 (Dose Expansion): Defined subject subgroups considered likely to respond to CB-03-10 (eg, relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, triple-negative breast adenocarcinoma) or indications that demonstrated activity in Part 1
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label, Multicenter, Phase 1 Study to Evaluate the Maximum Tolerated Dose of Orally Administered CB-03-10 With Dose Expansion Phase, in Subjects With Advanced Solid Tumors
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: 1
Part 1 (Dose Escalation): 100 mg daily.
Drug: CB-03-10
CB-03-10, 100 mg capsule for oral use




Primary Outcome Measures :
  1. Determine the maximum tolerated dose [ Time Frame: 30 days ]
    Determine the maximum tolerated dose (MTD) of CB-03-10 in subjects with advanced solid tumors

  2. Determine the dose-limiting toxicity [ Time Frame: 30 days ]
    Determine the dose-limiting toxicity (DLT) of CB-03-10 in subjects with advanced solid tumors


Secondary Outcome Measures :
  1. Determine a recommended Phase 2 dose (RP2D) of CB-03-10 [ Time Frame: 30 days ]
    Determine a recommended Phase 2 dose (RP2D) of CB-03-10

  2. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 30 days ]
    Determine the safety profile of CB-03-10 in subjects with advanced solid tumors

  3. Evaluate the activity response rate [ Time Frame: 30 days ]
    Evaluate the activity response rate of CB-03-10 in subjects with specific solid tumors (eg, relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, relapsed/refractory triple-negative breast adenocarcinoma)

  4. Cmax of CB-03-10 [ Time Frame: 30 days ]
    Cmax of CB-03-10

  5. AUC of CB-03-10 [ Time Frame: 30 days ]
    AUC of CB-03-10

  6. Cmax of CB-03-10 metabolite CB-03-05 [ Time Frame: 30 days ]
    Cmax of CB-03-10 metabolite CB-03-05

  7. AUC of CB-03-10 metabolite CB-03-05 [ Time Frame: 30 days ]
    AUC of CB-03-10 metabolite CB-03-05

  8. Evaluate the activity overall survival [OS] [ Time Frame: 30 days ]
    Evaluate the activity overall survival [OS] of CB-03-10 in subjects with specific solid tumors (eg, relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, relapsed/refractory triple-negative breast adenocarcinoma)

  9. Evaluate the activity progression-free survival [PFS] [ Time Frame: 30 days ]
    Evaluate the activity progression-free survival [PFS] of CB-03-10 in subjects with specific solid tumors (eg, relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, relapsed/refractory triple-negative breast adenocarcinoma)



Information from the National Library of Medicine

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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. Signed, informed consent
  2. For Part 1 (Dose Escalation): Histologically or cytologically confirmed relapsed or refractory advanced or metastatic solid tumor of any origin, not amenable to standard of care therapy.

    For Part 2 (Dose Expansion): Histologically or cytologically confirmed relapsed or refractory advanced or metastatic solid tumor (specific tumor types to be determined by the Safety Review Committee (SRC) at the conclusion of Part 1, but will likely include one of the following 3 categories: advanced androgen independent prostate adenocarcinoma, relapsed/refractory pancreatic adenocarcinoma, or relapsed/refractory TNBC not amenable to standard of care therapies with reasonable likelihood of significant clinical benefit.

  3. Age: ≥ 18 years.
  4. ECOG performance status ≤ 2.
  5. For Part 1 (Dose Escalation) measurable or evaluable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria For Part 2 (Dose Expansion): measurable disease as per RECIST 1.1 criteria
  6. Adequate hematology defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelets (PLT) ≥ 100 x 109/L
    3. Hemoglobin (Hb) ≥ 9.0 g/dl
  7. Adequate liver function defined as:

    1. Alanine aminotransferase (ALT) ≤ 3.0 x ULN (≤ 5 x the upper limit of normal [ULN] if liver involved with tumor)
    2. Aspartate aminotransferase (AST) ≤ 3.0 x ULN (≤ 5 x ULN if liver involved with tumor)
    3. Total bilirubin ≤ 1.5 mg/gL (except for subjects with Gilbert's syndrome in which ≤ 3 x ULN)
  8. Adequate renal function defined as:

    a. Creatinine ≤ 1.5 ULN or creatinine clearance ≥ 50 mL/min

  9. If previously treated, recovered from adverse effects from prior therapy (eg, chemotherapy) to ≤ Grade 1 (graded according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events, version 5.0 [CTCAE v.5.0]), except for the following:

    a. Alopecia (Grade 2 allowed)

  10. Negative pregnancy test for females of childbearing potential
  11. Commitment from subject to practice medically appropriate/acceptable method of birth control (eg, hormonal, condoms or other adequate barrier controls, intrauterine contraceptive device, or sterilization) beginning at the Screening Visit and continuing until 3 months following the last treatment with study drug
  12. Willingness and ability to comply with all study requirements

Exclusion Criteria:

  1. Pregnancy or breastfeeding
  2. Presence of active infections (eg, requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the Investigator, would place the patient at undue risk or interfere with the study, and/or requiring systemic therapy.
  3. Positive hepatitis B core antibody or surface antigen unless quantitative DNA PCR is negative and subject will be receiving prophylaxis for reactivation
  4. Positive hepatitis C virus on PCR
  5. Positive HIV antibody
  6. Known brain metastases or signs and/or symptoms suggestive of brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks.
  7. Known cancer of other primary origin within the prior 5 years (excluding Stage I non-melanoma skin cancer and prostate cancer controlled with hormonal therapy)
  8. Active autoimmune disease (ie, requiring therapy or anticipated to require therapy while participating in study).
  9. Cardiac disease as manifested by any of the following:

    1. > Grade II heart failure, graded per New York Heart Association (NYHA) criteria.
    2. Unstable angina pectoris
    3. Acute or subacute coronary syndromes, including myocardial infarction, occurring within 1 year prior to study treatment
    4. Arrhythmia needing continuous treatment
    5. Ejection fraction less than the institutional lower limit of normal as assessed by multigrated radionuclide angiography (MUGA) scan or echocardiogram
  10. Uncontrolled hypertension (ie, not on stable doses of antihypertensive medications for at least 1 month).
  11. Major surgery or trauma within 4 weeks prior to start of study treatment.
  12. Fewer than 28 days (or fewer than 5 half-lives, whichever is shorter) from prior anticancer therapy including chemotherapy, hormonal, investigational, and/or biological therapies except for ongoing hormonal therapy administered for control of cancer (eg, prostate cancer)
  13. Requirement for chronic corticosteroids or other immunosuppressant drugs. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
  14. Warfarin at doses greater than 1 mg/day or equivalent doses of other coumarin derivatives
  15. Participation in another interventional clinical trial
  16. Psychiatric illness/social situations that would interfere with compliance with study requirements
  17. Other severe medical or psychiatric conditions that would impart, in the judgement of the Investigator and/or Sponsor, excess risk to the subject during study participation

Additional Information:
Publications of Results:
Stringer EM, Saha P, Swoboda A, Kocherginsky M, Baker G, Olberkyte S, et al. A phase I trial of mifepristone (M), carboplatin (C), and gemcitabine (G) in advanced breast and ovarian cancer. J Clin Oncol. 2017;35 (15 sup(1083):1083.

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Responsible Party: Cosmo Technologies Ltd
ClinicalTrials.gov Identifier: NCT03863145     History of Changes
Other Study ID Numbers: CB-03-10/01
First Posted: March 5, 2019    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No