A Phase 2 Trial for Patients With Metastatic Solid Cancer
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|ClinicalTrials.gov Identifier: NCT04713371|
Recruitment Status : Recruiting
First Posted : January 19, 2021
Last Update Posted : June 21, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Metastatic Cancer||Drug: Keytruda Injectable Product Drug: Yervoy Injectable Product Drug: Cytoxan Procedure: Cryosurgical freezing (cryosurgery) Drug: GM-CSF Injectable||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Male or female subjects greater than 18 years of age with histologically- proven metastatic cancer with at least one imaging- or histologically- proven metastases to lymph nodes, bone, or soft tissue.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of Cryosurgical Freezing and Multiplex Immunochemotherapy in Patients With Metastatic Solid Cancer|
|Actual Study Start Date :||May 19, 2021|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2023|
Single arm. Subjects receiving treatment.
Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria.
Drug: Keytruda Injectable Product
Keytruda (pembrolizumab): PD-1 inhibitor antibody
Injectable 50mg/mL, only 2 mL injected.
Other Name: pembrolizumab
Drug: Yervoy Injectable Product
Yervoy (ipilimumab): Anti-CTLA-4 antibody
Injectable 5mg/mL, only 2 mL injected.
Other Name: ipilimumab
Injectable 250mg/m2, only 1 mL injected. Oral low dose cyclophosphamide: 50mg once daily pill for 5 days prior to first treatment, 3 days prior to 2nd and 3rd treatment.
Other Name: Cyclophosphamide
Procedure: Cryosurgical freezing (cryosurgery)
Cryosurgery, also known as cryoablation, for metastatic cancer works by freezing the cancer cells inside the tumor. Cryoablation will release intact antigens to prime the immune system.
Other Name: Cryoablation
Drug: GM-CSF Injectable
Daily injection administered subcutaneously. 250 mcg daily injections for a total of 25 days post after each treatment.
Other Name: Sargramostim
- Primary Endpoint: Efficacy [ Time Frame: baseline to 8 weeks after end of treatment (approximately 5 months)) ]Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by overall response rate of radiographic changes according to iRECIST criteria.
- Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy [ Time Frame: baseline to 8 weeks after end of treatment (approximately 5 months); ]Efficacy of Cryosurgical Freezing and Multiplex Immunochemotherapy as determined by RECIST1.1 criteria
- Radiographic progression-free survival (rPFS) [ Time Frame: baseline to 8 weeks after end of treatment (approximately 5 months); ]rPFS as determined with both RECISTS1.1 and iRECIST criteria.
- Best overall response of confirmed PR or CR by independent radiology review [ Time Frame: baseline to 8 weeks after end of treatment (approximately 5 months) ]Best overall response of confirmed PR or CR by independent radiology review
- Time to progression (TTP) based on independent radiology review [ Time Frame: baseline up to 8 weeks after last treatment ]Time to cancer progression is measured from the date of first study treatment until the date of cancer progression.
- Overall survival [ Time Frame: 3 years ]Number of participants that are alive.
- Incidence of AEs/SAEs [ Time Frame: baseline to 8 weeks after the last treatment ]Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
- Severity of AEs/SAEs [ Time Frame: baseline through 8 weeks after the last treatment ]Severity of AEs/SAEs
- Duration of AEs/SAEs [ Time Frame: baseline through 8 weeks after the last treatment ]Duration of AEs/SAEs
- The time to objective disease progression [ Time Frame: baseline through 8 weeks after the last treatment (Safety Follow-Up) ]Data will be collected for the design of future studies.
- Endpoint Evaluation [ Time Frame: Up to 8 weeks after final treatment of last patient enrolled ]Each of the endpoints will be evaluated after stratifying for site of cancer origin, histologic type, and cancer grade (W.H.O. grading)
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- Have exhausted all other standard therapies; Have failed available therapy or are not a candidate for, or refuse available therapy (i.e. concerned with high adverse events rate in available therapy or outcome worse than disease); or failure of prior chemotherapy.
- Histologically-documented solid cancer. All subjects must submit their primary tumor or metastatic 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 using iRECIST criteria and identified by radiographic imaging (Imaging should be current within the past three months of subject entering the study; if not repeat imaging must be done prior to enrollment.). In order to be eligible, the patient must have at least one metastatic bone and/or metastatic soft tissue site, lymph node site, and/or bone site with cancer mass measuring 1.0 cm or more in diameter based on soft tissue, lymph node, and/or bone lesions as defined by any of the following:
- Any soft tissue lesion defined by imaging deemed by the physician to be consistent with distant metastatic disease. For patients undergoing PSMA PET (prostate cancer patients only), only PSMA avid lesions that have a CT or MRI correlate consistent with metastasis will be counted as a site of metastasis.
- Metastatic lymph node disease defined by imaging. Any lymph node ≥ 1.5 cm in shortest dimension will be noted as involved with disease.
- 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 (prostate cancer patients only), only PSMA-avid lesions that are 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. Any subject 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 will also 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.
- NOTE: Women of child-bearing potential will be tested for pregnancy (which must be negative) before treatment is given. Acceptable range is < 5 mIU/mL
- No active major medical or psychological problems that could be complicated by study participation.
- Is currently participating in 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 bone metastasis as the only site of disease.
- 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 pembrolizumab) 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.
- Is taking any current medication known to interfere with serum PSA concentration or radiographic extent of cancer (e.g., Enzalutamide, hormonal therapy) within 30 days for non-depot or 90 days for depot of start of treatment.
- 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 a metastatic lesion in locations that is deemed by the investigator as high risk for procedure-related complications (e.g., bleeding, nerve and/or bowel damage) despite consideration of preventative techniques such as hydro-dissection with fluid to push away adjacent crucial structures.
- 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 recent (within 2 years) 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.
- Pregnant and/or expecting to bear or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed within 30 days.
- Personal representative (family member or friend) withholds consent for any reason.
- Unable for any reason to understand the consent form and other written information and freely give written informed consent.
- Score less than 12.0 (out of possible maximum of 20) on the UBACC Capacity to Consent Assessment Instrument.
- Hypersensitivity to Cyclophosphamide.
- Hypersensitivity to GM-CSF.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04713371
|Contact: Melanie Wilk, M.S.||email@example.com|
|United States, Michigan|
|Ascension Providence Rochester Hospital||Recruiting|
|Rochester, Michigan, United States, 48307|
|Contact: Mike Cribbs 248-652-5626 Michael.Cribbs@ascension.org|
|Principal Investigator:||David G Bostwick, M.D., M.B.A.||Rampart Health|
|Responsible Party:||Rampart Health, L.L.C.|
|Other Study ID Numbers:||
|First Posted:||January 19, 2021 Key Record Dates|
|Last Update Posted:||June 21, 2022|
|Last Verified:||June 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors