Investigating the Safety, Tolerability and Efficacy of Amorphous Calcium Carbonate (ACC) on the Treatment of Subjects With CRPC

NCT02864784 | Withdrawn Phase 1

• 1 other identifier: AMCS-ONCO-PR-001-CTIL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Studies objectives: To evaluate the safety, tolerability and efficacy of ACC given in combination with ZA or with Denosumab as compared to placebo given with ZA or with Denosumab as outline below:

• Safety and Tolerability:
• Adverse events (AEs) and serious AEs
• Safety laboratory measurements
• Hypercalcemic and hypercalciuric episodes
• Treatment withdrawal due to AEs and overall Efficacy:
• Skeletal Related Events (SREs)
• Measurable and evaluable disease progression
• Progression Free Survival (PFS)
• Pain assessment via the VAS scale

Conditions

Castrate Resistant Prostate Cancer With Bone Metastasis

Outcome Measures

Primary Outcomes (1)

• Changes in the number of Skeletal Related Events (SREs)

  Bone scan will take place at baseline and week 12

Secondary Outcomes (10)

• Time from randomization to onset of first SRE.

  Bone scan will be made on baseline and week 12

• Proportion of subjects (%) with SREs.

  Bone scan will take place at baseline and week 12

• Proportion of subjects (%) with evidence of measureable and evaluable disease progression or SREs.

  Bone scan will take place at baseline and week 12

• Progression Free Survival (PFS).

  CT or MRI will be assessed on screening and week 12

• Number of subjects that are receiving radiation as a rescue treatment

  An assessment will take place at week 2,4,6,8,10,12 16,20 and 24

Study Arms (2)

Amorphous calcium carbonate

EXPERIMENTAL

Subjects in this arm of the study will receive ACC tablets, containing 200 mg elemental calcium in addition to the standard treatment with ZA or Denosumab (4 mg once every 4 weeks for ZA and 120mg (1.7ml injection) every 4 weeks for Denosumab)

Drug: Amorphous calcium carbonate

Placebo

PLACEBO COMPARATOR

Subjects in this arm of the study will receive Placebo tablets in addition to standard treatment with ZA or Denosumab (4 mg once every 4 weeks for ZA and 120mg (1.7ml injection) every 4 weeks for Denosumab)

Other: Placebo

Interventions

Amorphous calcium carbonate DRUG

Subjects in this arm of the study will receive standard treatment with ZA or Denosumab (4 mg once every 4 weeks for ZA and 120mg (1.7ml injection) every 4 weeks for Denosumab) as well as AMOR-1 tablets, containing 200 mg elemental calcium per tablet, individually titrated up to the maximum level which does not induce grade 2 hypercalcemia.

Also known as: ACC

Amorphous calcium carbonate

Placebo OTHER

microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 year
• Histologic proof of Castrate Resistant Prostate Cancer with Bone Metastasis
• Systemic steroids are only allowed if needed for hormonal therapy
• Previous radiation therapy must have been completed more than four weeks prior to enrollment into this study, unless subjects are under radiotherapy as a rescue therapy. Subjects must have recovered from all side effects.
• The last dose of chemotherapy must have been completed at least four weeks prior to enrollment into this study, and subjects must have recovered from all side effects.
• Subjects must have a performance status of 0-2 by the ECOG Scale.
• Subjects must have pretreatment (obtained \< 7 days prior to treatment) granulocyte count of \> 2,000/μL, platelet count of \> 100,000/μL, WBC \> 3,000/μL, hemoglobin ≥ 10.0 g/dL, serum creatinine \< 1.5 mg/dL, bilirubin \< 1.5 mg/dL, and ALT/AST not more than 3x the upper limit of normal (or not more than 5x if the elevation is due to liver metastases).
• Subjects must be normo-calcemic upon study entry.
• Subjects must be Vitamin D sufficient upon study entry, which is defined as 25(OH)D serum level \>20 ng/mL (50 nmol/L) according to a document composed by the Food and Nutrition Board of the Institute of Medicine, USA. If the subject is Vitamin D insufficient or deficient, then a loading dose of Vitamin D3 will be administered as follows:
• If the serum 25(OH)D level is 12-20 ng/mL (30-50 nmol/L) then a loading oral dose of 50,000 IU of Vitamin D3 should be administered twice with 3-5 days in between the doses.
• If the serum 25(OH)D level is ≤ 12 ng/mL (30 nmol/L), then a loading oral dose of 50,000 IU of Vitamin D3 will be administered three times with 3-5 days in between the doses. Serum 25(OH)D levels will be checked 1-2 weeks following the last loading.
• Regardless of Vitamin D levels, all subjects will receive a daily maintenance dose of 1000 IU Vitamin D3, which should be taken in the morning with breakfast.
• Estimated life expectancy of \> 3 months.
• Subjects must be accessible for follow-up.
• Written informed consent will be obtained.

You may not qualify if:

• Concurrent treatment with acute anticancer therapy
• Hormonal and corticosteroid therapies for Skeletal Related Events are not allowed
• Sarcoidosis
• Hypercalcemia
• Hypophosphatemia
• Hypoparathyroidism/Hyperparathyroidism
• Major surgery within 4 weeks of anticipated inception of AMOR-1therapy
• Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of therapy
• Psychiatric disorders rendering subjects incapable of complying with the requirements of the protocol
• Any illness or condition deemed by the investigator to contra-indicate treatment with AMOR-1 or ZA or Denosumab
• Hypersensitivity to ZA or Denosumab or Abiraterone acetate or Enzalutamide, or to any bisphosphonates or to any of the following excipients: Mannitol and Sodium citrate.
• Active cancer treatment except hormonal

Sponsors & Collaborators

• Amorphical Ltd.: lead

Study Sites (1)

Soroka Medical Center

Beersheba, 84101, Israel

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2016
• First Posted: August 12, 2016
• Study Start: June 1, 2022
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)