A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors

NCT03601897 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: DCC-2036-01-003
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 14

Brief Summary

This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with paclitaxel designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in patients with advanced or metastatic solid tumors.

Conditions

Locally Advanced or Metastatic Solid Tumor

Keywords

rebastinib; paclitaxel; breast cancer; ovarian cancer; endometrial cancer; gynecological carcinosarcoma; malignant mixed Mullerian tumor (MMMT)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events

  Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE).

  Baseline up to 2.89 years

• Objective Response Rate (ORR) (Part 2 Expansion)

  Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.

  Baseline to PD or Death due to Any Cause (Up to 1.54 years)

Secondary Outcomes (7)

• Objective Response Rate (ORR) (Part 1 Escalation)

  Baseline to PD or Death due to Any Cause (Up to 0.92 years)

• Duration of Response (DOR)

  Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years)

• Time to Progression (TTP)

  First Dose of Study Drug to PD (Up to 2.61 years)

• Progression-free-survival (PFS)

  First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years)

• Overall Survival (OS)

  First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years)

Study Arms (11)

Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose escalation of rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in combination with paclitaxel administered by intravenous (IV) infusion at 80 mg/meter squared (m\^2) on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose escalation of rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in triple-negative breast cancer (TNBC). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in TNBC. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in inflammatory breast cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in inflammatory breast cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in ovarian cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in ovarian cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in endometrial cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in endometrial cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

EXPERIMENTAL

Dose expansion in gynecological carcinosarcoma (GCS). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.

Drug: Rebastinib; Drug: Paclitaxel

Interventions

Rebastinib DRUG

Administered orally

Also known as: DCC-2036

Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Paclitaxel DRUG

Paclitaxel administered by IV infusion at 80 mg/m\^2

Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥18 years of age at the time of informed consent
• Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
• Part 2
• Triple-negative and Stage IV inflammatory breast cancer
• Recurrent ovarian cancer
• Recurrent, metastatic or high-risk endometrial cancer
• Advanced (stage III or IV), or recurrent gynecological carcinosarcoma
• Homologous or heterologous type carcinosarcoma (malignant mixed Mullerian tumor \[MMMT\] allowed
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
• Able to provide an archival tumor tissue sample
• Adequate organ function and bone marrow reserve
• If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
• Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures

You may not qualify if:

• Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose
• Not recovered from prior-treatment toxicities to Grade ≤1
• Peripheral neuropathy of any etiology \>Grade 1
• Concurrent malignancy
• Known active central nervous system (CNS) metastases
• Use of systemic corticosteroids
• Known retinal neovascularization, macular edema or macular degeneration
• History or presence of clinically relevant cardiovascular abnormalities
• QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females
• Left ventricular ejection fraction (LVEF) \<50% at screening
• Arterial thrombotic or embolic events
• Venous thrombotic event
• Active infection ≥Grade 3
• Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (HBV), or active HCV infection
• Use of proton pump inhibitors

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (14)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

University of Colorado Denver- Anschutz Medical Center

Aurora, Colorado, 80045, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

The University of Kansas Clinical Research Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber

Boston, Massachusetts, 02215, United States

Location

Northwell Health/Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Women & Infants Hospital

Providence, Rhode Island, 02905, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Oncology Consultants- Texas Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Carcinosarcoma

Interventions

rebastinib; DCC-2036; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Trial terminated on May 23, 2022, due to development program termination.

Results Point of Contact

• Title: Clinical Trials
• Organization: Deciphera Pharmaceuticals, LLC

clinicaltrials@deciphera.com

785-830-2100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 26, 2018
• Study Start: October 25, 2018
• Primary Completion: May 23, 2022
• Study Completion: May 23, 2022
• Last Updated: December 27, 2024
• Results First Posted: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)