Paclitaxel +/− Cixutumumab for Esophageal Cancer

Not currently recruiting at 272 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two chemotherapy drugs, paclitaxel and cixutumumab, in treating esophageal or gastroesophageal junction cancer that has metastasized. Paclitaxel stops cancer cells from growing and spreading, while cixutumumab may block a protein essential for cancer cell growth. Participants will receive either paclitaxel alone or a combination of paclitaxel and cixutumumab. The trial seeks individuals who have already undergone one treatment for their metastatic esophageal cancer and are experiencing active disease progression. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining paclitaxel and cixutumumab for esophageal cancer is generally well-tolerated. In one study, more than half of the patients experienced serious side effects, but these were manageable. Common issues included hair loss and a low white blood cell count, which can weaken the body's ability to fight infections.

Paclitaxel alone is also commonly used in cancer treatment and tends to cause fewer problems like nausea and vomiting compared to other drugs. While no treatment is without risk, evidence suggests that most patients can handle these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a new approach to tackling esophageal cancer. Cixutumumab, when combined with paclitaxel, targets the insulin-like growth factor 1 receptor (IGF-1R), which is different from the usual chemotherapy that attacks rapidly dividing cells in general. This targeted approach could potentially enhance the effectiveness of the treatment and provide better outcomes for patients. Additionally, combining cixutumumab with paclitaxel might improve the response rate and survival compared to using paclitaxel alone, offering a promising new option for those battling this tough cancer.

What evidence suggests that this trial's treatments could be effective for esophageal cancer?

This trial will compare the effects of paclitaxel alone to the combination of paclitaxel and cixutumumab for treating advanced esophageal cancer. Research has shown that paclitaxel alone provides some benefit, though limited, with studies finding a slight increase in survival rates. For instance, one study reported that patients lived for a median of 274 days when treated with paclitaxel. In this trial, some participants will receive paclitaxel alone, while others will receive the combination of paclitaxel and cixutumumab. Previous studies indicated that adding cixutumumab to paclitaxel did not improve survival, with overall survival being about the same as with paclitaxel alone, and only small differences observed. Therefore, while paclitaxel has some effect, adding cixutumumab does not seem to enhance its effectiveness for this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Steven J Cohen

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

Platelets >= 100,000/mcL

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37104870/

A Randomized Phase II ECOG-ACRIN Trial The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10485278/

Paclitaxel With or Without Cixutumumab as Second-Line ... The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01142388

Study Details | NCT01142388 | Paclitaxel With or Without ... This randomized phase II trial studies how well paclitaxel with or without cixutumumab works in treating patients with esophageal cancer or gastroesophageal ...

4. jdc.jefferson.edu jdc.jefferson.edu/cgi/viewcontent.cgi?article=1251&context=medoncfp

Paclitaxel With or Without Cixutumumab as Second-Line ... Conclusion: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical ...

5. withpower.com withpower.com/trial/phase-3-esophageal-squamous-cell-carcinoma-8-2010-b6da0

Paclitaxel +/− Cixutumumab for Esophageal Cancer 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 ...

6. academic.oup.com academic.oup.com/oncolo/article-pdf/28/9/827/51436914/oyad096.pdf

Paclitaxel With or Without Cixutumumab as Second-Line ... The primary endpoint was not met, as this combination of agents did not significantly improve progression-free survival. • Since the time of ...

7. researchgate.net researchgate.net/publication/370339313_Paclitaxel_With_or_Without_Cixutumumab_as_Second-Line_Treatment_of_Metastatic_Esophageal_or_Gastroesophageal_Junction_Cancer_A_Randomized_Phase_II_ECOG-ACRIN_Trial

A Randomized Phase II ECOG-ACRIN Trial Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. Conclusion: The addition of ...