Evaluation of AP-002 in Patients With Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase 1/2 Dose Escalation Study of AP-002 In Patients With Advanced or Recurrent Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04143789
• Other study ID #: ALT-002-SRE-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 27, 2019
• Est. completion date: April 2021

Study information

• Verified date: October 2019
• Source: Altum Pharmaceuticals INC
• Contact: Dawn East, BSN,RN
• Phone: 9544330329
• Email: deast[@]altumpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 61
• Est. completion date: April 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• AP-002
Dose escalation

Locations

Country	Name	City	State
United States	Research Institution	Chicago	Illinois
United States	Investigational Site	Houston	Texas
United States	Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Altum Pharmaceuticals INC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Assessment	Number of participants with treatment-related adverse events (safety and tolerability) as assessed by CTCAE v4.0	Through study completion/ up to 18 months
Primary	Dose Assessment	Define the recommended phase 2 dose	Up to 6 months
Secondary	Efficacy Assessment	Estimation of anti-tumor activity per RESIST v1.1	Through study completion/ up to 18 months
Secondary	Efficacy Assessment	For patients with bone metastases, the time to new bone metastasis, progression of bone metastases, or other skeletal related events	Through study completion/ up to 18 months
Secondary	Pharmacokinetic Assessment	Estimation of pharmacokinetic profile by evaluating maximum plasma concentration [Cmax]	Through study completion/ up to 18 months