278 Participants Needed

Combination Chemotherapy for Advanced Cancer

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to find the highest tolerable dose of the combination of bevacizumab (Avastin) and temsirolimus (Torisel) that can be given with 1 of 3 other study drugs --carboplatin (Paraplatin), paclitaxel (Taxol), or sorafenib (Nexavar). The safety of these drug combinations will also be studied.

Will I have to stop taking my current medications?

The trial requires that you stop taking previous chemotherapy or radiotherapy for three weeks before joining, and six weeks if the therapy has delayed toxicity. Additionally, medications that strongly affect the enzyme P450 3A4 should be avoided within five half-lives of temsirolimus.

What data supports the effectiveness of the drug combination of Bevacizumab, Carboplatin, and Paclitaxel for advanced cancer?

The combination of Bevacizumab, Carboplatin, and Paclitaxel has been shown to improve overall survival in patients with advanced non-small cell lung cancer, as demonstrated in a clinical trial where patients receiving this combination lived longer than those receiving only Carboplatin and Paclitaxel.12345

What safety information is available for the combination chemotherapy treatment involving Bevacizumab, Carboplatin, and Paclitaxel?

The combination of Bevacizumab, Carboplatin, and Paclitaxel has been associated with serious side effects such as high blood pressure, bleeding, and infections. Some patients may experience severe complications like gastrointestinal perforation (a hole in the stomach or intestines), wound healing issues, and blood clots. Common side effects include fatigue, nausea, and headache.46789

How is the drug combination of Bevacizumab, Carboplatin, Paclitaxel, Sorafenib, and Temsirolimus unique for treating advanced cancer?

This drug combination is unique because it combines multiple agents that target cancer in different ways, including Bevacizumab, which inhibits blood vessel growth in tumors, and Temsirolimus, which blocks a protein that helps cancer cells grow. This multi-faceted approach may offer benefits over standard treatments that typically use fewer drugs.510111213

Research Team

MD Anderson Cancer Center

Shannon Westin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic cancer that's resistant to standard treatments, relapsed, or without beneficial standard options. Participants must have stable vital signs and organ function, not be on other experimental drugs, and agree to use contraception. Excluded are pregnant women, those with recent surgery or significant cardiovascular issues, uncontrolled hypertension, certain allergies to the study drugs or their components.

Inclusion Criteria

I can take care of myself but might not be able to do active work.
My organs are functioning normally.
Ability to understand and the willingness to sign a written informed consent document
See 8 more

Exclusion Criteria

I have a serious heart condition.
History of hypersensitivity to specific medications or components
I am allergic to carboplatin or its ingredients.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of bevacizumab and temsirolimus with either carboplatin, paclitaxel, or sorafenib. The treatment cycles are 21 or 28 days long, depending on the drug combination.

56 days
Visits on Days 1, 8, and 15 of each cycle

Dose Escalation

Participants are assigned to dose levels to determine the maximum tolerated dose. Dose escalation continues until the highest tolerable dose is found.

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment. CT or MRI scans are performed every 2-3 cycles, and after 6 months, every 4 cycles if deemed necessary.

4 weeks

Treatment Details

Interventions

  • Bevacizumab
  • Carboplatin
  • Paclitaxel
  • Sorafenib
  • Temsirolimus
Trial OverviewResearchers are testing the highest dose of Bevacizumab (Avastin) and Temsirolimus (Torisel) that can be safely given with one of three other drugs: Carboplatin (Paraplatin), Paclitaxel (Taxol), or Sorafenib (Nexavar). The aim is to determine safety and tolerability of these combinations in treating advanced cancers.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Sorafenib GroupExperimental Treatment3 Interventions
Sorafenib: Starting dose 200 mg by mouth daily for a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Group II: Paclitaxel GroupExperimental Treatment3 Interventions
Paclitaxel: Starting dose 30 mg/m2 given by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.
Group III: Carboplatin GroupExperimental Treatment3 Interventions
Carboplatin: Starting dose AUC 2 by vein on day 1 of a 21 day cycle. Temsirolimus: Starting dose 12.5 mg by vein given on day 1, 8, and 15 of a 21 day cycle. Bevacizumab: Starting dose 5 mg/kg given by vein on day 1 of a 21 day cycle.

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Findings from Research

The AVALUZ trial demonstrated that the combination of bevacizumab, gemcitabine, and paclitaxel resulted in a median progression-free survival of 12.3 months and a median overall survival of 27.4 months in previously untreated HER-2 negative breast cancer patients.
The treatment was generally well tolerated, with manageable adverse events, and showed that baseline circulating tumor cells and angiotensin type 1 receptor expression could predict patient responses and progression-free survival.
Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer.Salvador, J., Manso, L., de la Haba, J., et al.[2022]
In a phase III trial involving 1,043 patients with advanced nonsquamous non-small-cell lung cancer, the combination of bevacizumab with cisplatin and gemcitabine significantly improved progression-free survival (PFS) compared to placebo, with hazard ratios of 0.75 for low-dose and 0.82 for high-dose bevacizumab.
The treatment also resulted in higher objective response rates (34.1% for low-dose and 30.4% for high-dose bevacizumab) compared to placebo (20.1%), while maintaining a similar incidence of serious adverse events across all treatment groups.
Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.Reck, M., von Pawel, J., Zatloukal, P., et al.[2022]
Bevacizumab (Avastin) combined with carboplatin and paclitaxel significantly improves overall survival in patients with advanced nonsquamous non-small cell lung cancer, with a median survival of 12.3 months compared to 10.3 months for those receiving chemotherapy alone.
While bevacizumab shows efficacy, it is associated with a higher incidence of severe adverse events, including neutropenia and hypertension, and carries risks of serious complications like gastrointestinal perforation and pulmonary hemorrhage, highlighting the need for careful patient monitoring.
FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer.Cohen, MH., Gootenberg, J., Keegan, P., et al.[2022]

References

Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. [2022]
Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. [2022]
Carboplatin plus Weekly Paclitaxel Combined with Bevacizumab as First-line Treatment for Non-small Cell Lung Cancer. [2019]
FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. [2022]
Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer. [2021]
Safety and effectiveness of bevacizumab treatment for metastatic colorectal cancer: final results from the Avastin(®) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study. [2022]
Managing toxicities associated with antiangiogenic biologic agents in combination with chemotherapy for metastatic colorectal cancer. [2013]
Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. [2021]
Capecitabine and bevacizumab as first-line treatment in elderly patients with metastatic colorectal cancer. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Treatment of ovarian cancer: current status. [2015]
11.United Statespubmed.ncbi.nlm.nih.gov
Phase 2 study of S-1 and carboplatin plus bevacizumab followed by maintenance S-1 and bevacizumab for chemotherapy-naive patients with advanced nonsquamous non-small cell lung cancer. [2022]
Paclitaxel plus carboplatin versus paclitaxel plus alternating carboplatin and cisplatin for initial treatment of advanced ovarian cancer: long-term efficacy results: a Hellenic Cooperative Oncology Group (HeCOG) study. [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. [2015]