A Phase 2 Trial for Men With Metastatic Prostatic Adenocarcinoma

NCT04090775 | Completed Phase 2 FDA Drug

• 1 other identifier: ABSCOPAL 1001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This study seeks to estimate the occurrence of adverse events related to the study treatment (Cryosurgical freezing and Intratumoral Combination Immunotherapy), as well as determine the potential efficacy.

Conditions

Metastatic Prostatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Primary endpoint: PSA decline

  Primary Endpoint: Efficacy of cryosurgical freezing and intratumoral combination immunotherapy as determined by the proportion of patients achieving serum PSA decline from baseline of at least 50%.

  baseline to 8 weeks after end of treatment (approximately 6 months)

Secondary Outcomes (1)

• Efficacy of cryosurgical freezing and intratumoral combination immunotherapy iRECIST criteria

  baseline to 8 weeks after end of treatment (approximately 6 months)

Other Outcomes (8)

• Efficacy of cryosurgical freezing and intratumoral combination immunotherapy RECIST 1.1 Criteria

  baseline to 8 weeks after end of treatment (approximately 6 months); quarterly up to one year; and thereafter biannually for up to 2 more years.

• Radiographic progression-free survival (rPFS)

  baseline to 8 weeks after end of treatment (approximately 6 months); quarterly up to one year; and thereafter biannually for up to 2 more years.

• Best overall response of confirmed PR or CR by independent radiology review

  From signing of Informed Consent form, approximately every 4 weeks for the first 3 months; quarterly up to one year; and thereafter biannually for up to 2 more years.

Study Arms (1)

Single arm. Subjects receiving treatment.

OTHER

Cryosurgical freezing and intratumoral combination immunotherapy as determined by the proportion of patients achieving serum PSA decline from baseline of at least 50%.

Drug: Opdivo Injectable Product; Drug: Yervoy Injectable Product; Drug: Cytoxan; Procedure: Cryosurgical freezing (cryosurgery)

Interventions

Opdivo Injectable Product DRUG

Opdivo (nivolumab): PD-1 inhibitor antibody Injectable 10mg/mL, only 1 mL injected.

Also known as: nivolumab

Single arm. Subjects receiving treatment.

Yervoy Injectable Product DRUG

Yervoy (ipilimumab): Anti-CTLA-4 antibody Injectable 5mg/mL, only 1 mL injected.

Also known as: ipilimumab

Single arm. Subjects receiving treatment.

Cytoxan DRUG

Cytoxan (cyclophosphamide): Chemotherapy agent Both Injectable and Oral low dose: Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: option of either 50mg once daily pill or 25mg twice daily pill for two weeks on, then two weeks off, then two weeks on again.

Also known as: Cyclophosphamide

Single arm. Subjects receiving treatment.

Cryosurgical freezing (cryosurgery) PROCEDURE

Cryosurgery, also known as cryoablation, for prostate cancer works by freezing the cancer cells inside the prostate gland. Cryoablation will release intact antigens to prime the immune system.

Also known as: Cryoablation

Single arm. Subjects receiving treatment.

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• Have a performance status of 0-3 on the ECOG Performance Scale.
• Have a life expectancy of 6 months or more as determined by treating physician.
• Not a candidate for or refuses chemotherapy; or failure of prior chemotherapy.
• PSA \>2 ng/mL at baseline.
• Available archival tumor tissue for correlative studies. Submission of archival TRUS prostate biopsy tissue is required if available, in the form of representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or at least 15 slides, with an associated pathology report. If archival prostate tissues are unavailable or cannot be obtained, a repeat TRUS prostate biopsy is not required for eligibility.
• Histologically-documented adenocarcinoma or mixed adenocarcinoma-neuroendocrine carcinoma of the prostate. All subjects must submit their primary tumor or metastatic biopsy pathology specimens and laboratory and imaging reports to Rampart Health where they will be centrally reviewed. Central Rampart Health pathologic review is not required for screening but rather for confirmation of diagnosis and histologic subtype of cancer. Local pathologic review is sufficient for eligibility determination.
• Measurable disease as defined by PCWG3 using iRECIST criteria and identified by radiographic imaging. In order to be eligible, the patient must have at least one metastatic bone and/or metastatic lymph node site(s) with cancer mass measuring 1 cm or more in diameter based on bone and/or soft tissue lesions as defined by any of the following:
• Bone metastases defined by bone imaging. If the patient has technetium bone scan, and/or NaF PET performed, either study may be used for documenting metastases; both scans do not need to show the number of metastases required for study entry. For patients undergoing PSMA PET, only PSMA avid lesions that are consistent with metastasis will be counted as a site of metastasis.
• Distant metastatic lymph node disease defined by imaging. A lymph node ≥1 cm in shortest dimension will be noted as involved with disease. Distant metastatic lymph nodes will be determined as any lymph nodes outside the confines of the true pelvis. For patients undergoing PSMA PET, only PSMA avid lesions that are consistent with metastasis will be counted as a site of metastasis.
• Any other soft tissue lesion defined by imaging deemed by the physician to be consistent with distant metastatic disease. For patients undergoing PSMA PET, only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
• The effects of the medications in this protocol on the developing human fetus are unknown. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the first dose of study therapy, for the duration of the study participation, and for 120 days after the last dose of study therapy.
• Their partners should be encouraged to use proper method of contraception.
• Acceptable initial laboratory values within 14 days of treatment initiation according to the following: ANC ≥ 1500/µl; Hemoglobin ≥ 9.0 g/dL(prior transfusion permitted); Platelet count ≥ 100,000/µl; Creatinine ≤ 2.0 x the institutional upper limit of normal (ULN) OR creatinine clearance \>30 ml/min; Potassium ≥ 3.5 mmol/L (within institutional normal range); Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's disease); SGOT (AST) ≤ 2.5x ULN, or \<5x ULN in patients with documented liver metastases; SGPT (ALT) ≤ 2.5x ULN or \<5x ULN in patients with documented liver metastases; Albumin \>2.5 mg/dL; Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Deviation from these values is allowed at the discretion of the treating investigator.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days prior to the first dose of trial treatment, with the exception of steroids for adrenal insufficiency in which case prednisone \<10mg/day or its equivalent is allowed.
• Has a performance status of 4-5 on the ECOG Performance Scale.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to monoclonal antibodies such as nivolumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Persisting toxicity related to prior therapy (NCI CTCAE v.5 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, Grade 2 anemia, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include carcinoid, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs), including but not limited to systemic or cutaneous lupus erythematosus, cutaneous psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, sicca syndrome, polymyalgia rheumatica, polyarteritis nodosa, granulomatous polyangiitis, microscopic polyangiitis, polyarteritis nodosa, temporal arteritis, giant cell arteritis, dermatomyositis, Kawasaki disease. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, hydroxychloroquine, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorder or any other condition that would interfere with cooperation with the requirements of the trial in the opinion of the Physician-investigator.

Sponsors & Collaborators

• Rampart Health, L.L.C.: lead

Study Sites (2)

Antelope Valley Urology & Incontinence

Lancaster, California, 93534, United States

Location

Ascension Providence Rochester Hospital

Rochester, Michigan, 48307, United States

Location

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Cyclophosphamide; Cryosurgery

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• David G Bostwick, M.D.,M.B.A.

  Rampart Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Male subjects greater than 18 years of age with histologically-proven cancer of the prostate with at least one imaging- or histologically -proven metastasis to lymph nodes or bone.

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: September 16, 2019
• Study Start: June 28, 2019
• Primary Completion: July 30, 2020
• Study Completion: January 31, 2022
• Last Updated: June 21, 2022

Record last verified: 2022-02

Locations

US (2)