Clinical Trials /

Evaluation of AP-002 in Patients With Solid Tumors

NCT04143789

Description:

The purpose of this trial is to define an effective and safe dose of AP-002 in advanced or recurrent solid tumors for which there are no standard therapies to use in subsequent studies in advanced or recurrent breast, non-small cell lung cancer (NSCLC) or prostate cancers.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of AP-002 in Patients With Solid Tumors
  • Official Title: A Phase 1/2 Dose Escalation Study of AP-002 In Patients With Advanced or Recurrent Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ALT-002-SRE-01
  • NCT ID: NCT04143789

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
AP-002no other namesTablets to be taken orally daily for 14 of 21 day cycle

Purpose

The purpose of this trial is to define an effective and safe dose of AP-002 in advanced or recurrent solid tumors for which there are no standard therapies to use in subsequent studies in advanced or recurrent breast, non-small cell lung cancer (NSCLC) or prostate cancers.

Detailed Description

      The Phase 1 portion of this study will determine the Pharmacodynamically Active Dose (PAD) of
      AP-002 in humans, defined as the dose at which the plasma concentration of AP-002, as
      measured by Ga, is 300-500 ng/mL and which is at or below the Maximum Tolerated Dose (MTD),
      to use in the clinical setting of advanced or recurrent solid tumors. This will be followed
      by a Phase 2 expanded cohort treated at the PAD, to estimate the efficacy of AP-002 in
      patients with advanced or recurrent breast cancer, NSCLC and prostate cancer.

      Patients will receive AP-002 orally, once daily for 14 days of a 21 day cycle.
    

Trial Arms

NameTypeDescriptionInterventions
Tablets to be taken orally daily for 14 of 21 day cycleExperimentalAP-002 (4 mg and 20 mg tablets) to be taken orally daily for 14 days
  • AP-002

Eligibility Criteria

        Inclusion Criteria:

          1. Phase 1: Patients with advanced or recurrent solid tumors with target (± non-target)
             or with only non-target disease, for which there is no standard therapy available
             Phase 2: Patients with advanced or recurrent breast cancer, NSCLC, or prostate cancer
             with target (± non-target) or with only non-target disease for which there is no
             standard therapy available

          2. Patients with bone metastases but without target disease are eligible

          3. Patients with bone metastases must have at least one bone lesion that has not received
             radiation therapy within 6 weeks prior to Cycle 1 Day 1

          4. Patients must discontinue bisphosphonate and/or denosumab treatment.

          5. Age ≥ 18 years

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          7. O2 saturation ≥ 92% on room air per pulse oximetry

          8. Exhaled nitrous oxide ≤ 50 parts per billion (ppb)

          9. Adequate hematologic, hepatic and renal function defined as:

               1. Hemoglobin ≥ 9 g/dL

               2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

               3. Platelet count ≥ 75 × 109/L

               4. Total bilirubin ≤ 2 × upper limit of normal (ULN). Patients with an established
                  diagnosis of Gilberts syndrome with an unconjugated bilirubin ≤ 2 mg/dL and
                  conjugated bilirubin within normal limits (WNL) are eligible.

               5. Serum electrolytes WNL

               6. Transaminases ≤ 3 × ULN

               7. Prothrombin time (PT)/international normalized ratio (INR), thromboplastin time
                  (PTT), or activated PTT (aPTT) ≤ 1.5 × ULN. For patients on therapeutic coumadin,
                  PT (INR) ≤ 2.5 × ULN is acceptable; for patients on therapeutic heparin, PTT (or
                  aPTT) ≤ 2.5 × ULN

               8. Corrected creatinine clearance ≥ 40 mL/minute, based on the Cockcroft-Gault
                  equation

         10. Patient must have discontinued prior antineoplastic therapy at least 21 days prior to
             Cycle 1 Day 1 and have recovered or stabilized from any prior AEs related to the prior
             therapy

         11. Provision of signed and dated informed consent form

         12. Serum 25-hydroxyvitamin D ≥ 30 ng/mL by investigative site laboratory at screening

        Exclusion Criteria:

          1. Evidence of benign primary hyperparathyroidism, hyperthyroidism, adrenal
             insufficiency, vitamin D intoxication, mild alkali syndrome, sarcoidosis or other
             granulomatous disease

          2. Treatment with calcitonin, mithramycin or cinacalcet within 7 days prior to the date
             of the screening

          3. Receiving dialysis for renal failure

          4. Patients with a known history of clinically significant active infection, including
             human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

          5. Patients with active central nervous system (CNS) metastases are not eligible, but
             patients with treated, stable CNS metastases are allowed

          6. Patients with QT interval of ≥ 480 msec on ECG

          7. Patients with Paget's disease of bone

          8. Patients of childbearing potential unwilling to abstain from sexual intercourse, or
             employ effective barrier methods of contraception during participation in this trial

          9. Pregnancy or lactation. A negative pregnancy test will be required for women of
             childbearing potential prior to study enrollment and will be repeated throughout the
             study. Women of childbearing potential will be defined as women who have not had
             natural or pharmacologic menopause, nor surgical sterilization.

         10. Patients unwilling or unable to take oral medication, requiring a nasogastric or
             gastrostomy tube, or unwilling to adhere to the treatment regimen and fasting
             requirements

         11. Patients unwilling to comply with all study procedures or who are unavailable for the
             duration of the study

         12. Known allergies to any components of the AP-002 Drug Product
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety Assessment
Time Frame:Through study completion/ up to 18 months
Safety Issue:
Description:Number of participants with treatment-related adverse events (safety and tolerability) as assessed by CTCAE v4.0

Secondary Outcome Measures

Measure:Efficacy Assessment
Time Frame:Through study completion/ up to 18 months
Safety Issue:
Description:Estimation of anti-tumor activity per RESIST v1.1
Measure:Efficacy Assessment
Time Frame:Through study completion/ up to 18 months
Safety Issue:
Description:For patients with bone metastases, the time to new bone metastasis, progression of bone metastases, or other skeletal related events
Measure:Pharmacokinetic Assessment
Time Frame:Through study completion/ up to 18 months
Safety Issue:
Description:Estimation of pharmacokinetic profile by evaluating maximum plasma concentration [Cmax]

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Altum Pharmaceuticals INC

Last Updated

October 30, 2019