Vitamin D3 + Chemotherapy + Bevacizumab for Colorectal Cancer

(SOLARIS Trial)

Recruiting at 1061 trial locations

Overseen By Jun Gong

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

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: 6

Duration: Up to 5 years

455 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if vitamin D3 along with regular cancer drugs and another drug that helps the immune system can better treat colorectal cancer that has spread. Vitamin D3 may help the body use essential minerals, making the cancer drugs more effective. Vitamin D3 has been shown to slow down cancer cell growth and help them mature, and it has been effective in reducing intestinal tumors in animal studies.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. You must stop taking vitamin D supplements, thiazide diuretics (like hydrochlorothiazide), and some other medications like oral corticosteroids, lithium, phenytoin, quinidine, isoniazid, and rifampin at least 7 days before joining the trial. Check with the trial team for specific guidance on your medications.

What evidence supports the effectiveness of the drug combination of Vitamin D3, chemotherapy, and Bevacizumab for colorectal cancer?

Research shows that adding Bevacizumab to chemotherapy regimens like fluorouracil and leucovorin significantly improves survival and slows tumor progression in patients with advanced colorectal cancer. Irinotecan, another component of the treatment, is also effective against advanced colorectal cancer when combined with these drugs. ^{1 2 3 4 5}

Is the combination of Vitamin D3, chemotherapy, and Bevacizumab safe for colorectal cancer treatment?

Bevacizumab, when combined with chemotherapy drugs like fluorouracil, leucovorin, and irinotecan, has been shown to improve survival in colorectal cancer patients, but it can cause side effects like blood clots, high blood pressure, bleeding, and gastrointestinal perforation (a hole in the stomach or intestines). ^{2 5 6 7 8}

What makes the drug combination of Vitamin D3, chemotherapy, and Bevacizumab unique for colorectal cancer?

This treatment is unique because it combines Vitamin D3, which may inhibit cancer growth by affecting blood vessel formation, with Bevacizumab, a drug that targets and blocks the growth of new blood vessels needed by tumors. This combination aims to enhance the effectiveness of standard chemotherapy drugs like fluorouracil and irinotecan, potentially improving outcomes for patients with metastatic colorectal cancer. ^{5 9 10 11 12}

Research Team

Kimmie Ng, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with advanced colorectal cancer that has spread, who haven't had treatment for metastatic disease. They should have finished any previous chemotherapy over a year ago and not be planning surgery to remove the cancer. Participants need measurable disease, no genetic mutations like dMMR or MSI-H, and can't have uncontrolled illnesses or be on certain medications.

Inclusion Criteria

Urine protein to creatinine (UPC) ratio =< 1 mg/dL OR urine protein =< 1+

I have completed my rectal cancer radiation treatment more than 4 weeks ago.

My cancer does not have a known genetic mismatch repair issue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy, bevacizumab, and vitamin D3. Cycles repeat every 14 days for up to 5 years.

Up to 5 years

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 6 months

Treatment Details

Interventions

• Bevacizumab
• Cholecalciferol
• Fluorouracil
• Irinotecan
• Irinotecan Hydrochloride
• Leucovorin Calcium

Trial Overview The study tests if high-dose vitamin D3 combined with standard chemotherapy (leucovorin calcium, fluorouracil, oxaliplatin, irinotecan hydrochloride) and bevacizumab (a monoclonal antibody) improves outcomes in metastatic colorectal cancer compared to usual treatments.

Participant Groups

Group I: Arm I (bevacizumab, chemotherapy, high-dose vitamin D3) Experimental Treatment 9 Interventions

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV on days 1-3 or irinotecan hydrochloride IV on day 1, leucovorin calcium IV over 90 minutes on day 1, and fluorouracil IV on days 1-3. Patients also receive high-dose cholecalciferol PO QD on days 1-14. Cycles repeat every 14 days for 5 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (bevacizumab, chemotherapy, standard-dose vitamin D3) Active Control 9 Interventions

Patients receive bevacizumab and chemotherapy as in Arm I. Patients also receive standard-dose cholecalciferol PO QD on days 1-14. Cycles repeat every 14 days for 5 years 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?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase IV trial involving 209 treatment-naïve patients with metastatic colorectal cancer, the combination of bevacizumab and FOLFIRI resulted in a median progression-free survival (PFS) of 11.1 months and a median overall survival (OS) of 22.2 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse events being mild (grade 1/2), while serious side effects like neutropenia and venous thromboembolic events occurred in over 10% of patients, indicating manageable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Sobrero, A., Ackland, S., Clarke, S., et al.[2022]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

Bevacizumab, a monoclonal antibody that targets VEGF, significantly improves response rates, time to tumor progression, and overall survival in patients with advanced colorectal cancer when added to fluorouracil-based chemotherapy regimens, based on two clinical trials.

While bevacizumab shows efficacy in treating advanced colorectal cancer, it is associated with serious safety concerns, including thromboembolic events, hypertension, hemorrhage, and gastrointestinal perforation, highlighting the need for careful monitoring and further studies comparing its effectiveness with other chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab for advanced colorectal cancer. Hadj Tahar, A.[2013]

In a study of 1,401 patients with metastatic colorectal cancer, adding bevacizumab to first-line oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was longer in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, indicating that while bevacizumab helps delay disease progression, it may not necessarily extend overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

In a study involving 1,401 patients with metastatic colorectal cancer, adding bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was slightly better in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, and the response rates were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

Bevacizumab, a targeted therapy that inhibits vascular endothelial growth factor, significantly improves treatment outcomes in metastatic colorectal cancer when added to standard chemotherapy, showing a higher objective response rate (40% vs. 17%) and longer median survival (21.5 months vs. 13.8 months).

While bevacizumab is associated with manageable safety concerns such as hypertension and thrombosis, its efficacy in extending time to disease progression (9.0 months vs. 5.2 months) highlights its potential as a valuable addition to colorectal cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy of colorectal cancer: clinical experience with bevacizumab. Fernando, NH., Hurwitz, HI.[2019]

In a combined analysis of three studies involving 490 patients, the addition of bevacizumab to FU/LV treatment resulted in a median overall survival of 17.9 months, compared to 14.6 months for the control group, indicating a significant survival benefit.

Patients receiving FU/LV with bevacizumab also experienced improved progression-free survival (8.8 months vs. 5.6 months) and a higher response rate (34.1% vs. 24.5%), demonstrating the efficacy of bevacizumab in treating metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. Kabbinavar, FF., Hambleton, J., Mass, RD., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. [2022]

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

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. [2022]

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

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]

4. England pubmed.ncbi.nlm.nih.gov

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Bevacizumab for advanced colorectal cancer. [2013]

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

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. [2023]

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

Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of capecitabine, irinotecan, and bevacizumab in patients with previously untreated metastatic colorectal cancer. [2018]

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

A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Targeted therapy of colorectal cancer: clinical experience with bevacizumab. [2019]

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

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. [2022]