Octreotide + Interferon/Bevacizumab for Neuroendocrine Tumors

Recruiting at 557 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Octreotide

Must not be taking: Interferon, Bevacizumab

Disqualifiers: Brain tumor, Hypertension, Hemolytic anemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 23

Duration: 21 days per cycle

427 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies octreotide acetate and recombinant interferon alfa-2b to see how well it works compared to octreotide acetate and bevacizumab in treating patients with high-risk neuroendocrine tumors that have spread to other places in the body (metastatic) or spread from where it started to nearby tissue or lymph nodes (locally advanced). Octreotide acetate and recombinant interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of cancer. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving octreotide acetate together with recombinant interferon alfa-2b is more effective than giving octreotide acetate together with bevacizumab in treating patients with neuroendocrine tumor.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not plan to use any other concurrent chemotherapy, immunotherapy, or certain other treatments while on the trial.

What data supports the effectiveness of the drug combination of Octreotide, Interferon, and Bevacizumab for treating neuroendocrine tumors?

The combination of Octreotide and Bevacizumab showed a longer time to treatment failure compared to Octreotide and Interferon, with a confirmed radiologic response rate of 12% for Bevacizumab. Additionally, combining Interferon and Octreotide in patients who did not respond to Octreotide alone resulted in a 77% biochemical response, indicating some effectiveness in managing symptoms. ^{1 2 3 4 5}

Is the combination of Octreotide, Interferon, and Bevacizumab safe for treating neuroendocrine tumors?

The combination of Octreotide with either Interferon or Bevacizumab has been studied for neuroendocrine tumors. Common side effects with Bevacizumab include high blood pressure, protein in urine, and fatigue, while with Interferon, they include fatigue, low white blood cell count, and nausea. The combination of Interferon and Octreotide is generally well-tolerated, with flu-like symptoms and fatigue being the most common side effects. ^{1 2 6 7 8}

How is the drug combination of Octreotide, Interferon, and Bevacizumab unique for treating neuroendocrine tumors?

This drug combination is unique because it combines Octreotide, which controls hormone secretion, with Interferon, which has direct anti-tumor effects and boosts the immune system, and Bevacizumab, which inhibits blood vessel growth in tumors. This multi-faceted approach aims to manage symptoms and potentially slow tumor progression in neuroendocrine tumors. ^{1 2 4 6 8}

Research Team

James C Yao

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with advanced neuroendocrine tumors that can't be removed by surgery, are not just in the bones, and haven't spread to the brain. Participants should have a certain level of physical fitness (Zubrod status 0-2) and adequate organ function. They must not have had certain treatments like interferon or bevacizumab before, but one prior chemotherapy regimen is okay. Pregnant or breastfeeding individuals cannot join, and effective birth control is required for those who can conceive.

Inclusion Criteria

My blood clotting tests are within normal ranges.

I have had treatments targeting specific cancer growth factors before.

Urine protein must be screened by urine analysis for Urine Protein Creatinine (UPC) ratio

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either depot octreotide plus bevacizumab or depot octreotide plus interferon. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Visits every 21 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 2-6 months.

Up to 3 years

Follow-up visits every 2-6 months

Treatment Details

Interventions

• Bevacizumab
• Octreotide Acetate
• Recombinant Interferon Alfa-2b

Trial Overview The study compares two treatments: octreotide acetate with recombinant interferon alfa-2b versus octreotide acetate with bevacizumab to see which is better at slowing down cancer growth in high-risk patients with metastatic or locally advanced neuroendocrine tumors.

Participant Groups

Group I: Arm II (octreotide acetate and recombinant interferon alfa-2b) Experimental Treatment 3 Interventions

Patients receive octreotide acetate IM as in arm I on day 1 and recombinant interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, and 19. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (octreotide acetate and bevacizumab) Experimental Treatment 3 Interventions

Patients receive depot octreotide acetate IM and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 2 trial involving 50 patients with advanced neuroendocrine tumors (NETs), the combination of everolimus and octreotide LAR demonstrated an objective response rate of 18%, with 92% of patients achieving clinical benefit (complete response, partial response, or stable disease).

The treatment was generally well tolerated, with most adverse events being mild (grade 1 or 2), indicating that this combination therapy could be a safe and effective first-line option for patients with NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study. Bajetta, E., Catena, L., Fazio, N., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Interferon-alpha versus somatostatin or the combination of both in gastro-enteropancreatic tumours. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination? [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Octreotide acetate long-acting release in patients with metastatic neuroendocrine tumors pretreated with lanreotide. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study. [2015]

8. Denmark pubmed.ncbi.nlm.nih.gov

Dramatic response of a metastatic carcinoid tumour to a combination of interferon and octreotide. [2019]