Combining Palbociclib and Sunitinib for treating advanced solid tumors

A Phase 1b/2 Open Label, Dose Escalating, Single Center Study to Evaluate the Safety, Tolerability and Initial Efficacy of Palbociclib + Sunitinib Oral Kinase Inhibitor Combination as a Treatment for Advanced Solid Tumors

This study is testing if a combination of two cancer drugs, Palbociclib and Sunitinib, can help people with advanced solid tumors that haven't responded to other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rabin Medical Center (other)
• Drugs / interventions: Sunitinib
• Locations: 1 site (Petah Tikva)
• Trial ID: NCT06940349 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of a combination of Palbociclib and Sunitinib in patients with advanced solid tumors that are refractory to standard therapies. It is a single-arm, phase 1b/2 study that involves a dose escalation and expansion approach, where participants will take the drug combination daily for five days followed by two days off in a 28-day cycle. The study aims to include 20-100 patients with various types of Stage IV incurable metastatic solid tumors who have previously failed at least one standard treatment. Participants will undergo regular clinic visits for monitoring and dose adjustments as needed.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with Stage IV incurable metastatic solid tumors who have failed previous treatments.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced solid tumors that have not responded to existing therapies.

How similar studies have performed: While the combination of these specific drugs has not been extensively tested together, similar approaches in targeting advanced solid tumors have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

* Age ≥18 years
* Patients with Stage IV incurable/refractory metastatic solid tumors or locally advanced incurable/refractory tumor, who have one of the following tumor types:

  (1) Gastric adenocarcinoma, (2) Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal cancer (FIGO classification), (3) Breast cancer, (4) NSCLC, (5) Colorectal cancer, (6) Cholangiocarcinoma, (7) Pancreatic cancer, (8) Carcinosarcoma (any tissue origin), (9) High grade Neuroendocrine Carcinoma, from any tissue origin, (10) Sarcoma, all histological types, (11) Any other solid tumor.
* Patients who have failed all other appropriate lines of therapy or who have refused treatment(s) of choice
* Life expectancy of greater than 8 weeks
* Clinical performance status of ECOG 0-2
* Able to understand and sign the Informed Consent Form
* Must be able to adhere to the study visit schedule and other protocol requirements.

Hematology criteria:

Absolute neutrophils count greater than 1000/mm3 without support of filgrastim Normal WBC (\>3000/mm3). Hemoglobin greater than 8.0 g/dL Platelet count greater than 80,000/mm3

* Serology:
* Seronegative for HIV antibody
* Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test
* Patients with active HBV must have:
* HBV DNA \< 500 IU/mL obtained within 28 days prior to initiation of study treatment
* received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
* Patients with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV
* Chemistry:
* Serum ALT/AST less than three times the upper limit of normal (ULN)/ less than five times ULN if liver metastasis present
* Serum creatinine less than or equal to 1.6 mg/dL
* Total bilirubin no more than x1.5 times the ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dL.
* Non-pregnant (via negative pregnancy test)/non-breast-feeding women and women with no intention to become pregnant/to breast-feed during the term of the trial and for at least three months after cessation of the P+S treatment
* More than 14 days must have elapsed since any prior systemic therapy before day 1, and patients' toxicities must have recovered to a Grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures, local radiotherapy with the past two weeks, as long as all toxicities have recovered to Grade 1 or less.

Exclusion Criteria:

* Inclusion Criteria:

  * Age ≥18 years
  * Patients with Stage IV incurable/refractory metastatic solid tumors or locally advanced incurable/refractory tumor, who have one of the following tumor types:

    (1) Gastric adenocarcinoma, (2) Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal cancer (FIGO classification), (3) Breast cancer, (4) NSCLC, (5) Colorectal cancer, (6) Cholangiocarcinoma, (7) Pancreatic cancer, (8) Carcinosarcoma (any tissue origin), (9) High grade Neuroendocrine Carcinoma, from any tissue origin, (10) Sarcoma, all histological types, (11) Any other solid tumor.
  * Patients who have failed all other appropriate lines of therapy or who have refused treatment(s) of choice
  * Life expectancy of greater than 8 weeks
  * Clinical performance status of ECOG 0-2
  * Able to understand and sign the Informed Consent Form
  * Must be able to adhere to the study visit schedule and other protocol requirements
  * Hematology:
* Absolute neutrophils count greater than 1000/mm3 without support of filgrastim
* Normal WBC (\>3000/mm3).
* Hemoglobin greater than 8.0 g/dL
* Platelet count greater than 80,000/mm3

  • Serology:
* Seronegative for HIV antibody
* Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test
* Patients with active HBV must have:
* HBV DNA \< 500 IU/mL obtained within 28 days prior to initiation of study treatment
* received anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
* Patients with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV

  • Chemistry:
* Serum ALT/AST less than three times the upper limit of normal (ULN)/ less than five times ULN if liver metastasis present
* Serum creatinine less than or equal to 1.6 mg/dL
* Total bilirubin no more than x1.5 times the ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dL.

  * Non-pregnant (via negative pregnancy test)/non-breast-feeding women and women with no intention to become pregnant/to breast-feed during the term of the trial and for at least three months after cessation of the P+S treatment
  * More than 14 days must have elapsed since any prior systemic therapy before day 1, and patients' toxicities must have recovered to a Grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures, local radiotherapy with the past two weeks, as long as all toxicities have recovered to Grade 1 or less.

Exclusion Criteria:

* Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis, atypical mycobacterial disease, and herpes zoster), human immunodeficiency virus (HIV), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) or oral antibiotics within 1 week of day 1
* History of severe immediate hypersensitivity reaction to any of the agents used in this study
* Uncontrolled hypertension
* Proteinuria \>3 grams per day
* Subjects who have received any investigational drug or used investigational device within two weeks preceding screening
* Active consumption of illicit drugs within one month preceding screening
* Serious psychiatric or psychological disorders
* Patients with significant cardiac, respiratory or active malignancy disease comorbidities.
* Women of child-bearing potential who intend to become pregnant or breast-feed or who are pregnant or breastfeeding

Where this trial is running

Petah Tikva

• Davidoff cancer center, RMC — Petah Tikva, Israel (RECRUITING)

Study contacts

• Principal investigator: idit Peretz, MD,MBA — Rabin Medical Center
• Study coordinator: Idit Peretz, MD, MBA

Conditions: Solid Tumors Refractory to Standard Therapy, COPS study, phase 1/phase 2 study, combination Palbociclib and Sutent