Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies
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| ClinicalTrials.gov Identifier: NCT04902040 |
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Recruitment Status :
Recruiting
First Posted : May 26, 2021
Last Update Posted : February 13, 2023
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Sponsor:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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Brief Summary:
This phase Ib/II trial studies the side effects and best dose of plinabulin in combination with radiation therapy and immunotherapy in patients with select cancers that have spread to other places in the body (advanced) after progression on PD-1 or PD-L1 targeted antibodies. Plinabulin blocks tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving plinabulin in combination with radiation therapy and immunotherapy may work better in treating advanced cancers.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Bladder Carcinoma Advanced Lung Non-Small Cell Carcinoma Advanced Malignant Solid Neoplasm Advanced Melanoma Advanced Merkel Cell Carcinoma Advanced Renal Cell Carcinoma Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage III Merkel Cell Carcinoma AJCC v8 Clinical Stage IV Cutaneous Melanoma AJCC v8 Clinical Stage IV Merkel Cell Carcinoma AJCC v8 Pathologic Stage III Cutaneous Melanoma AJCC v8 Pathologic Stage III Merkel Cell Carcinoma AJCC v8 Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8 Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8 Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 Pathologic Stage IIID Cutaneous Melanoma AJCC v8 Pathologic Stage IV Cutaneous Melanoma AJCC v8 Pathologic Stage IV Merkel Cell Carcinoma AJCC v8 Stage III Bladder Cancer AJCC v8 Stage III Lung Cancer AJCC v8 Stage III Renal Cell Cancer AJCC v8 Stage IIIA Bladder Cancer AJCC v8 Stage IIIA Lung Cancer AJCC v8 Stage IIIB Bladder Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Stage IIIC Lung Cancer AJCC v8 Stage IV Bladder Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IV Renal Cell Cancer AJCC v8 Stage IVA Bladder Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Bladder Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 | Biological: Atezolizumab Drug: Avelumab Biological: Durvalumab Biological: Nivolumab Biological: Pembrolizumab Drug: Plinabulin Radiation: Radiation Therapy | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 12 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label, Single-Center, Phase 1b/2 Study to Evaluate the Safety of Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Malignancies After Progression on PD-1 or PD-L1 Targeted Antibodies |
| Actual Study Start Date : | April 14, 2021 |
| Estimated Primary Completion Date : | June 1, 2025 |
| Estimated Study Completion Date : | June 1, 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (radiation therapy, plinabulin, immunotherapy)
Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients receive plinabulin IV over 30-60 minutes on days 1 and 4 of cycle 1, days 1 and 4 of cycle 2 (if receiving radiation therapy in cycle 2), and day 1 and or 15 (any day receiving immunotherapy) of subsequent cycles. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
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Biological: Atezolizumab
Given IV
Other Names:
Drug: Avelumab Given IV
Other Names:
Biological: Durvalumab Given IV
Other Names:
Biological: Nivolumab Given IV
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Drug: Plinabulin Given IV
Other Name: NPI-2358 Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
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Active Comparator: Arm B (radiation therapy, immunotherapy)
Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
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Biological: Atezolizumab
Given IV
Other Names:
Drug: Avelumab Given IV
Other Names:
Biological: Durvalumab Given IV
Other Names:
Biological: Nivolumab Given IV
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
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Primary Outcome Measures :
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days after last dose of plinabulin ]AEs will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
- Objective tumor response rate (ORR) (complete response + partial response) [ Time Frame: Up to 4 years ]Radiologic evaluations will be performed at screening and every 9 weeks (± 1 week) for 27 weeks (during Q3W dosing) or every 8 weeks (± 1 week) for 24 weeks (during Q4W dosing), then every 12 weeks during treatment cycles in the Treatment Phase regardless of treatment cycles and follow up period. Categorization of response will be based on both immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) and modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Secondary Outcome Measures :
- Disease control rate (complete response, partial response + stable disease) [ Time Frame: Up to 4 years ]Assessed according to irRECIST criteria.
- Progression-free survival [ Time Frame: From the first study dose date to the date of first documentation of confirmed disease progression or death (whichever occurs first), assessed up to 4 years ]Will be analyzed using Kaplan-Meier method or Cox regression.
- Overall survival [ Time Frame: From the start date of the treatment period until date of death from any cause, assessed up to 4 years ]Will be analyzed using Kaplan-Meier method or Cox regression.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Subjects must have one of seven histologically or cytologically confirmed malignant neoplasms (non-small cell lung cancer, small cell lung cancer, renal cell cancer, bladder cancer, Merkle cell cancer, microsatellite instability high (MSI-H) cancer (any histology), and melanoma) progressed on previous anti-PD-1/PD-L1 mAb treatment +/- chemotherapy or anti-CTLA4 requiring further treatment
- At least one lesion is amenable to radiation
- At least one additional non-contiguous lesion that has not been irradiated amenable to radiographic evaluation
- Have measurable disease based on immune-related response criteria (immune-related Response Evaluation Criteria In Solid Tumors [RECIST])
- Tissue must be newly obtained as a core needle biopsy (not fine-needle aspiration [FNA]) of the lesion being evaluated
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Subjects must be recovered from any prior major surgery. The major surgery must be performed at least 4 weeks prior to consent date
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Platelets >= 100 x 10^9/L
- Transfusions and growth factors are allowed
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Hemoglobin >= 9 g/dL
- Transfusions and growth factors are allowed
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Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Transfusions and growth factors are allowed
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White blood cell (WBC) >= 3 x 10^9/L
- Transfusions and growth factors are allowed
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (=< 1.5 x ULN if alkaline phosphatase is > 2.5 x ULN) (In the expansion cohort, subjects with known liver involvement may have ALT =< 5 x ULN)
- Alkaline phosphatase < 4 x ULN
- Total bilirubin =< 1 x ULN (In the expansion cohort, subjects with Gilbert's syndrome [hereditary indirect hyperbilirubinemia] who must have a total bilirubin of =< 3 x ULN)
- Albumin >= 3 g/dL
- Renal function defined as a calculated or measured glomerular filtration rate (GFR) >= 30 mL/min and Cockcroft-Gault equation
- The patient has recovered to grade =< 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of =< grade 2 specified elsewhere in these inclusion criteria
- Subjects must give informed consent according to the rules and regulations of the individual participating sites
- Negative urine pregnancy test in women of child bearing potential within 7 days of first dose of treatment and subjects of child-bearing potential must agree to use effective contraception during and for 5 months following the last dose of atezolizumab or nivolumab, and for 4 months after the last dose of pembrolizumab, and for 3 months after last dose of durvalumab and avelumab, and for 3 months after your last dose of plinabulin. A woman of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable or mechanical contraception; women who are single and women whose male sexual partners have been vasectomized or whose male sexual partners have received or are utilizing mechanical contraceptive devices
Exclusion Criteria:
- Evidence of complete or partial bowel obstruction
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Subjects with primary central nervous system (CNS) tumor or CNS tumor involvement. However, subjects with metastatic CNS tumors may participate in this study if the patient is:
- > 4 weeks from prior therapy completion
- Clinically stable with respect to the CNS tumor at the time of study entry
- Not receiving steroid therapy in treating CNS tumor or CNS tumor involvement
- Not receiving anti-convulsive medications (that were started for brain metastases)
- Need of total parenteral nutrition
- Allergic to any of anti-PD-1/PD-L1 monoclonal antibody (mAb) intended to receive
- Prior exposure to plinabulin
- Pregnancy or lactation
- Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) =< 3 weeks prior to study drug administration date
- Chemotherapy, or immunotherapy or any other systemic anticancer therapy =< 3 weeks prior to study drug administration date except anti-PD-1/PD-L1 mAb mono or combination therapy
- Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated)
- Major surgery within four weeks before consent date
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Unstable cardiovascular function or active cardiac disease:
- Symptomatic ischemia (chest pain of cardiac origin),or
- Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on antiarrhythmics are excluded; 1st degree AV block or asymptomatic Left anterior fascicular block (LAFB)/ right bundle branch block (RBBB) will not be excluded),or
- Congestive heart failure (CHF) of New York Heart Association (NYHA) class >= 3, or
- Myocardial infarction (MI) within 3 months of consent date
- Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the patient is clinically stable
- Subject is known to be positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
- Significantly diseased (as determined by the PI or treating physician) or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. Presence of ileus or other significant gastrointestinal disorder known to predispose to ileus or chronic bowel hypomotility
- Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date
- Concurrent therapy with approved or investigational anticancer therapeutics
- Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Men whose partner is a woman of child-bearing potential, (i.e. biologically able to conceive), and who is not employing two forms of highly effective contraception. Highly effective contraception (e.g. male condom with spermicide, diaphragm with spermicide, intra-uterine device) must be used by both sexes during the study and must be continued for 5 months following the last dose of atezolizumab or nivolumab, for 4 months after the last dose of pembrolizumab, and for 3 months after last dose of durvalumab and avelumab, and for 3 months after your last dose of plinabulin. Women of child-bearing potential is defined as sexually mature women who are not surgically sterile or who have not been naturally postmenopausal for at least 12 consecutive months (e.g., who has had menses any time in the preceding 12 consecutive months)
Information from the National Library of Medicine
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): NCT04902040
Locations
| United States, Texas | |
| M D Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Vivek Subbiah 713-563-1930 CCTTNewPtTeam@mdanderson.org | |
| Principal Investigator: Vivek Subbiah | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
| Principal Investigator: | Vivek Subbiah | M.D. Anderson Cancer Center |
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT04902040 |
| Other Study ID Numbers: |
2020-0296 NCI-2021-03489 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2020-0296 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | May 26, 2021 Key Record Dates |
| Last Update Posted: | February 13, 2023 |
| Last Verified: | January 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell Carcinoma Lung Neoplasms Melanoma Urinary Bladder Neoplasms Carcinoma, Renal Cell Skin Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases |
Respiratory Tract Diseases Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas Urologic Neoplasms Urogenital Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Urinary Bladder Diseases Urologic Diseases Male Urogenital Diseases Adenocarcinoma |