Plinabulin + Radiation/Immunotherapy for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Anticonvulsants

Disqualifiers: CNS tumor, Pregnancy, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 21

Duration: Up to 4 years

19 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Siqing FU, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with certain advanced cancers that have worsened after treatment with PD-1 or PD-L1 inhibitors. Participants must be in fair health (ECOG 0-2), have at least one tumor suitable for radiation, and adequate organ function. Pregnant women, those with recent major surgery, uncontrolled infections, or heart disease are excluded.

Inclusion Criteria

I have at least one cancer spot that hasn't been treated with radiation and can be seen on scans.

Your absolute neutrophil count is at least 1.5 billion per liter.

Subjects must give informed consent according to the rules and regulations of the individual participating sites

Exclusion Criteria

I have not had an untreated infection in the week before starting treatment.

Treatment with an investigational anti-cancer study drug within 3 weeks prior to study drug administration date

Medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive plinabulin in combination with radiation therapy and immunotherapy. Radiation therapy is administered on days 1-3, 1-4, or 1-5 of cycle 1, with potential additional radiation in cycle 2. Plinabulin is given IV on specific days, and immunotherapy is administered according to the specific drug schedule. Cycles repeat every 21 or 28 days.

Up to 4 years

Visits every 21 or 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 12 months.

12 months

Annual visits

Treatment Details

Interventions

• Atezolizumab
• Avelumab
• Durvalumab
• Nivolumab
• Pembrolizumab
• Plinabulin
• Radiation Therapy

Trial Overview The study is testing the combination of plinabulin (a drug that targets blood vessels to tumors) with radiation therapy and immunotherapy drugs like Pembrolizumab. The goal is to find the best dose of plinabulin and see if this combo can better treat advanced cancers than current methods.

Participant Groups

Group I: Arm A (radiation therapy, plinabulin, immunotherapy) Experimental Treatment 7 Interventions

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.

Group II: Arm B (radiation therapy, immunotherapy) Active Control 6 Interventions

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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+