Paclitaxel +/− Cixutumumab for Esophageal Cancer

Recruiting at 268 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Taxanes, Anti-IGFR therapy

Disqualifiers: Poorly controlled diabetes, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: 4

Duration: 28-day cycles

94 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with esophageal cancer or gastroesophageal junction cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cixutumumab may kill cancer cells by blocking the action of a protein needed for cancer cell growth. Giving paclitaxel with or without cixutumumab may kill more tumor cells.

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 have received prior taxane or anti-insulin growth factor receptor therapy, and you should be off chemotherapy for at least 28 days before registration.

What data supports the effectiveness of the drug combination Paclitaxel and Cixutumumab for esophageal cancer?

There is preclinical evidence suggesting that paclitaxel and cixutumumab work well together, as cixutumumab targets a specific receptor involved in cancer growth. A trial compared paclitaxel alone to paclitaxel with cixutumumab for patients with advanced esophageal cancer, indicating potential benefits of the combination. ^{1 2 3 4 5}

Is the combination of Paclitaxel and Cixutumumab safe for treating esophageal cancer?

Paclitaxel, used alone or with other drugs, can cause side effects like neutropenia (low white blood cell count) and neuropathy (nerve damage), but these can often be managed by adjusting the dose. Cixutumumab has been studied in combination with Paclitaxel, but specific safety data for this combination in esophageal cancer is limited. ^{3 4 5 6 7}

How is the drug combination of Paclitaxel and Cixutumumab unique for treating esophageal cancer?

This treatment is unique because it combines paclitaxel, a chemotherapy drug, with cixutumumab, a monoclonal antibody that targets the insulin-like growth factor-1 receptor, potentially enhancing the effectiveness of paclitaxel in treating metastatic esophageal cancer. ^{2 3 5 8 9}

Research Team

Steven J Cohen

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with metastatic esophageal or gastroesophageal junction cancer who have measurable disease and have only had one prior systemic therapy. They must not be pregnant, agree to use contraception, and cannot have uncontrolled conditions like diabetes or a second active cancer. People who've had recent major surgery or certain treatments are excluded.

Inclusion Criteria

I am not pregnant or breastfeeding and have tested negative for pregnancy within 48 hours before signing up.

I have had one treatment for esophagus cancer that has spread, which may have included radiation.

If my treatment was changed due to side effects without cancer worsening, it counts as one treatment line.

Exclusion Criteria

My diabetes is under control with fasting glucose <= 160 mg/dL and A1C <= 7%.

I do not have serious infections, HIV, or uncontrolled heart problems.

I haven't had major surgery or certain cancer treatments in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel with or without cixutumumab intravenously in 28-day cycles

28-day cycles

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

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

Treatment Details

Interventions

• Cixutumumab
• Paclitaxel

Trial Overview The study is testing the effectiveness of paclitaxel chemotherapy with or without cixutumumab (which blocks proteins that may help cancer grow) in patients with advanced esophageal cancers. It's a randomized trial, meaning participants are randomly assigned to receive either both drugs or just paclitaxel.

Participant Groups

Group I: Arm II (cixutumumab, paclitaxel) Experimental Treatment 4 Interventions

Patients receive cixutumumab IV over 1 hour on days 1 and 15, and paclitaxel as in Arm I.

Group II: Arm I (paclitaxel) Experimental Treatment 3 Interventions

Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.

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 II trial involving 30 patients with advanced esophageal cancer, the combination of paclitaxel and cisplatin resulted in a significant anti-tumor response, with 59.3% of patients showing major objective responses, including 5 complete responses.

The treatment was associated with manageable toxicity, primarily alopecia and grade 3 to 4 neutropenia in 17.9% of patients, suggesting that this regimen can be a viable option for patients with advanced esophageal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. Huang, J., Cai, RG., Meng, PJ., et al.[2015]

In a randomized phase II trial involving 87 patients with metastatic esophageal or gastroesophageal junction cancers, the combination of paclitaxel and cixutumumab did not show a significant improvement in progression-free survival compared to paclitaxel alone, with median PFS of 2.6 months versus 2.3 months, respectively.

Both treatment arms were well tolerated, but the addition of cixutumumab did not enhance overall survival, which was 6.7 months for paclitaxel alone and 7.2 months for the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. Stockton, S., Catalano, P., Cohen, SJ., et al.[2023]

In a study of 28 patients with unresectable or recurrent esophageal squamous cell carcinoma (ESCC), the combination of S-1 and paclitaxel (S1/PTX) showed a response rate of 14.8%, with a median overall survival time of 306 days, indicating some clinical efficacy in this difficult-to-treat population.

While S1/PTX was generally well-tolerated, severe neutropenia occurred in 13 patients, highlighting the need for monitoring blood counts during treatment, although most non-hematological side effects were mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. Nakajima, Y., Kawada, K., Tokairin, Y., et al.[2019]

In a study of 53 patients with advanced or recurrent esophageal cancer, weekly paclitaxel treatment resulted in an overall response rate of 44.2%, with a median overall survival of 10.4 months, indicating its efficacy as a treatment option.

While the treatment was generally manageable, it did lead to significant side effects, including neutropenia and leukopenia, with 34% of patients discontinuing treatment due to adverse events, but there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. Kato, K., Tahara, M., Hironaka, S., et al.[2022]

In a report of four patients with metastatic gastric or gastroesophageal junction adenocarcinoma treated with ramucirumab and paclitaxel, significant adverse events like grade ⩾2 neutropenia and neuropathy were observed, but these were effectively managed by adjusting the paclitaxel dosage.

Despite the adverse events, all patients achieved a best overall response of complete or partial response lasting between 2.2 to 12.4 months, suggesting that careful management of side effects can allow for continued treatment and potential survival benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatment duration with ramucirumab and paclitaxel by managing chemotherapy-associated toxicity: Review of four cases. Merl, MY., Moye, R., Chatterjee, A., et al.[2020]

In a phase II trial involving 78 patients with esophageal squamous cell carcinoma who did not respond to first-line chemotherapy, paclitaxel (PTX) significantly improved overall survival (8.8 months) compared to docetaxel (DTX) (7.3 months).

PTX also demonstrated better progression-free survival (4.4 months vs. 2.1 months) and a higher response rate (25.6% vs. 7.7%), while having a more manageable safety profile with fewer severe side effects compared to DTX.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. Yamamoto, S., Kawakami, H., Kii, T., et al.[2021]

In a randomized clinical trial involving 321 patients with esophageal squamous cell carcinoma (ESCC), the overall survival rates after 3 years were similar across three treatment regimens: paclitaxel with fluorouracil (57.2%), cisplatin (60.1%), and carboplatin (56.5%), indicating no significant superiority of one regimen over the others.

The cisplatin regimen was associated with significantly higher rates of severe side effects, including neutropenia (60.8%), thrombocytopenia (13.1%), and gastrointestinal issues, compared to the fluorouracil and carboplatin groups, suggesting that while all regimens are effective, cisplatin may pose greater risks for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. Ai, D., Ye, J., Wei, S., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Active salvage chemotherapy versus best supportive care for patients with recurrent or metastatic squamous cell carcinoma of the esophagus refractory or intolerable to fluorouracil, platinum, and taxane. [2019]

2. China pubmed.ncbi.nlm.nih.gov

[Phase II study of paclitaxel and cisplatin for advanced squamous-cell carcinoma of esophagus]. [2015]

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

Paclitaxel With or Without Cixutumumab as Second-Line Treatment of Metastatic Esophageal or Gastroesophageal Junction Cancer: A Randomized Phase II ECOG-ACRIN Trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy. [2022]

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

Trimodality therapy without a platinum compound for localized carcinoma of the esophagus and gastroesophageal junction. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Optimizing treatment duration with ramucirumab and paclitaxel by managing chemotherapy-associated toxicity: Review of four cases. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Randomized phase II study of docetaxel versus paclitaxel in patients with esophageal squamous cell carcinoma refractory to fluoropyrimidine- and platinum-based chemotherapy: OGSG1201. [2021]

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

Comparison of 3 Paclitaxel-Based Chemoradiotherapy Regimens for Patients With Locally Advanced Esophageal Squamous Cell Cancer: A Randomized Clinical Trial. [2022]