Added protocol and synthetic subject data for NCT01797120

data/protocol/NCT01797120/README.md

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+# Synthetic Subject Data for NCT01797120
+
+synthetic subject data for the breast cancer study NCT01797120 using the results published on clinicaltrials.gov (NCT01797120-results.fhir.json)
+
+
+## Summary
+
+| Metric                    | Target        | Actual        |
+|---------------------------|---------------|---------------|
+| Subjects (FULEV / FULPL)  | 66 / 65       | 66 / 65 ✓     |
+| PFS events FULEV          | 39            | 39 ✓          |
+| PFS events FULPL          | 50            | 50 ✓          |
+| ORR FULEV                 | 18.2%         | 18.8% ✓       |
+| ORR FULPL                 | 12.3%         | 12.7% ✓       |
+| CBR FULEV                 | 63.6%         | 68.8% (~close)|
+| CBR FULPL                 | 41.5%         | 49.2% (~close)|
+
+
+**CBR = CR + PR + SD ≥ 24 weeks**
+
+Where:
+CR — Complete Response: all target lesions disappear
+PR — Partial Response: ≥30% decrease in sum of lesion diameters
+SD — Stable Disease: neither CR/PR nor progression, sustained for at least 24 weeks (≈6 months)
+
+The published targets for this trial were:
+
+| Arm                           | CBR                           |
+|-------------------------------|-------------------------------|
+| Fulvestrant + Everolimus      | 63.6% (42/66)                 |
+| Fulvestrant + Placebo         | 41.5% (27/65)                 |
+
+
+The small Clinical Benefit Rate (CBR) overcount comes from the 2+4 "still on treatment" subjects (who remain in the EFFFL population) being assigned responses from the CBR-sized pool. PFS events and ORR hit their targets exactly.
+
+Output files in *_test_data/_*:
+
+| File              | Rows              | Content                           |
+|-------------------|-------------------|-----------------------------------|
+| DM.csv            | 131               | Demographics, arm, site, dates    |
+| EX.csv            | 2,099             | Fulvestrant IM doses + everolimus/placebo daily records |
+| LB.csv            | 19,068            | CBC, chemistry, lipids at every visit |
+| VS.csv            | 6,810             | BP, HR, temp, weight at every visit |
+| TU.csv            | 610               | RECIST target lesion diameters at imaging visits |
+| RS.csv            | 328               | Overall disease response at each assessment |
+| ADSL.csv          | 131               | Subject-level PFS/OS times, events, response flags |
+| ADTTE.csv         | 254               | One PFS + one OS record per treated subject |
+
+

data/protocol/NCT01797120/results/NCT01797120-results.md

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+# NCT01797120 (PrE0102) — FHIR Bundle Summary
+
+Source: `docs/NCT01797120-results.fhir.json`
+
+---
+
+## Study Overview
+
+| Field | Value |
+|---|---|
+| Title | Study of Fulvestrant +/- Everolimus in Post-Menopausal, HR+ Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy |
+| Acronym | PrE0102 |
+| Phase | II |
+| Design | Randomized, Double-Blind, Placebo-Controlled, Parallel Cohort |
+| Status | Completed |
+| Sponsor | PrECOG, LLC (with Novartis as industry collaborator) |
+| Study Chair | Noah S Kornblum, MD (Saint Barnabas Cancer Center / Montefiore Medical Center) |
+| Publication | Journal of Clinical Oncology, June 2018 (PMID: 29664714) |
+| Study Period | May 2013 – September 2017 |
+
+---
+
+## Study Design & Arms
+
+1:1 randomization, stratified by:
+- ECOG Performance Status (0 vs. 1)
+- Measurable disease (yes vs. no)
+- Prior chemotherapy for metastatic disease (yes vs. no)
+
+| Arm | n | Treatment |
+|---|---|---|
+| Active | 66 | Fulvestrant 500 mg IM (Day 1 & 15, Cycle 1; then Day 1 q28d) + Everolimus 10 mg PO daily |
+| Control | 65 | Fulvestrant 500 mg IM (same schedule) + Placebo (2 tablets daily) |
+
+Maximum 12 cycles (48 weeks). Patients without disease progression after 12 cycles were
+unblinded and could continue at the same doses until progression or unacceptable toxicity.
+Patients on placebo crossed over to everolimus after unblinding.
+
+---
+
+## Eligibility Criteria
+
+### Inclusion
+- Postmenopausal female, age ≥ 18
+- Histologically/cytologically confirmed breast adenocarcinoma, Stage IV or inoperable
+  locally advanced
+- ER and/or PR positive; HER2/neu negative or equivocal
+- Aromatase inhibitor (AI) resistant: relapsed during adjuvant AI, or progressive disease
+  during AI for metastatic disease
+- ECOG Performance Status 0–1
+- ≤ 1 prior chemotherapy regimen for metastatic disease
+- Adequate organ function: WBC ≥ 3.0 × 10⁹/L, Hgb ≥ 9 g/dL, bilirubin ≤ 1.5× ULN,
+  LFTs ≤ 2.5× ULN, creatinine ≤ 1.5× ULN, cholesterol ≤ 300 mg/dL,
+  triglycerides ≤ 2.5× ULN
+
+### Exclusion
+- Prior mTOR inhibitor therapy
+- Brain metastases or leptomeningeal disease
+- Rapid progressive or life-threatening metastases
+- Major surgery within 4 weeks of randomization
+- Systemic corticosteroids ≥ 5 mg prednisone equivalent daily
+- Investigational agent within 4 weeks
+- Anticancer treatment within 4 weeks (bisphosphonates and GnRH analogs permitted)
+- Hypersensitivity to everolimus or fulvestrant
+- Gastrointestinal impairment affecting drug absorption
+- Severe uncontrolled comorbidities: CHF NYHA Class III–IV, unstable angina, MI within
+  6 months, uncontrolled diabetes, active infections, cirrhosis
+- Active hepatitis B or C without documented clearance
+
+---
+
+## Endpoints
+
+| Priority | Measure | Definition | Timeframe |
+|---|---|---|---|
+| Primary | Progression-Free Survival (PFS) | Time to progression per RECIST v1.0 (≥20% increase in target lesion sum, non-target lesion worsening, or new lesions) or death | Every 3 months, up to 3 years |
+| Secondary | Clinical Benefit Rate (CBR) | Proportion with CR, PR, or stable disease ≥ 24 weeks per RECIST v1.0 | Every 3 months, up to 3 years |
+| Secondary | Objective Response Rate (ORR) | Proportion with CR or PR per RECIST v1.0 | Every 3 months, up to 3 years |
+| Secondary | Overall Survival (OS) | Time to death from any cause; characterised by Kaplan-Meier | Every 3 months, up to 3 years |
+
+---
+
+## Key Results
+
+### Primary Endpoint — Median PFS
+
+| Arm | n | Median PFS | 95% CI |
+|---|---|---|---|
+| Fulvestrant + Everolimus | 66 | **10.3 months** | 7.6–13.8 months |
+| Fulvestrant + Placebo | 65 | **5.1 months** | 3.0–8.0 months |
+
+### Clinical Benefit Rate
+
+| Arm | n | CBR | 95% CI |
+|---|---|---|---|
+| Fulvestrant + Everolimus | 66 | **63.6%** | 50.9%–75.1% |
+
+---
+
+## Enrollment & Participant Flow
+
+**Total enrolled:** 131 patients (66 active / 65 control)
+
+### Discontinuation Reasons
+
+| Reason | Everolimus Arm (n=66) | Placebo Arm (n=65) |
+|---|---|---|
+| Adverse events | 37 | 49 |
+| Lack of efficacy | 13 | 5 |
+| Withdrawal by subject | 3 | 0 |
+| Protocol violation | 1 | 0 |
+| Death | 2 | 1 |
+| Other | 6 | 6 |
+| Not recorded | 2 | 4 |
+
+---
+
+## Baseline Characteristics
+
+| Characteristic | Everolimus Arm | Placebo Arm | Total |
+|---|---|---|---|
+| n | 66 | 65 | 131 |
+| Median age (years) | 64 (range 39–92) | 59 (range 35–85) | 63 (range 35–92) |
+| Sex | All female | All female | All female |
+| White | — | — | 64 |
+| Black | — | — | 8 |
+| Other | — | — | 2 |
+| Not specified | — | — | 57 |
+
+---
+
+## Study Sites (25 sites, United States)
+
+| # | Site | Location |
+|---|---|---|
+| 1 | Marin Cancer Care | Greenbrae, CA |
+| 2 | Stanford University | Stanford, CA |
+| 3 | SwedishAmerican Regional Cancer Center | Rockford, IL |
+| 4 | McFarland Clinic, PC | Ames, IA |
+| 5 | Johns Hopkins University | Baltimore, MD |
+| 6 | St. Joseph Mercy Hospital (MI Cancer Consortium) | Ann Arbor, MI |
+| 7 | Metro MN | Saint Louis Park, MN |
+| 8 | Missouri Valley Cancer Consortium | Omaha, NE |
+| 9 | Beth Israel | New York, NY |
+| 10 | Montefiore Medical Center | The Bronx, NY |
+| 11 | Ohio State University Medical Center | Columbus, OH |
+| 12 | Toledo COP | Toledo, OH |
+| 13 | Hematology & Oncology Associates of Northeastern PA | Dunmore, PA |
+| 14 | Penn State University | Hershey, PA |
+| 15 | Thomas Jefferson University | Philadelphia, PA |
+| 16 | Fox Chase Cancer Center | Philadelphia, PA |
+| 17 | University of Pittsburgh – Magee Women's Hospital | Pittsburgh, PA |
+| 18 | Reading Hospital – McGlinn Family Regional Cancer Center | West Reading, PA |
+| 19 | Main Line Health System | Wynnewood, PA |
+| 20 | University of Texas Southwestern | Dallas, TX |
+| 21 | Charleston Area Medical Center (CAMC) | Charleston, WV |
+| 22 | St. Vincent Hospital | Green Bay, WI |
+| 23 | Gundersen Health System | La Crosse, WI |
+| 24 | ProHealth Care Inc. | Waukesha, WI |
+| 25 | Aurora Cancer Care | Wauwatosa, WI |
+
+Sites are concentrated in the mid-Atlantic and Midwest regions, with community oncology
+representation alongside major academic medical centres.
+
+---
+
+## FHIR Bundle Structure
+
+**Bundle type:** `collection` | **Timestamp:** 2026-04-10 | **Total entries:** 22
+
+| Resource Type | Count | Purpose |
+|---|---|---|
+| `ResearchStudy` | 1 | Study metadata, design, eligibility, contacts |
+| `EvidenceVariable` | 20+ | Interventions, outcomes, and analysis variables |
+| `Group` | 4+ | Comparison group and eligibility definitions |
+| `Location` | 25 | Study sites with geocoordinates |
+| `Composition` | 5 | Structured results reports |
+| `Evidence` | 75+ | Statistical results (medians, CIs, rates) |
+| `PractitionerRole` | 1 | Study contact details |
+
+The bundle conforms to the `http://hl7.org/fhir/uv/ebm` evidence-based medicine profiles
+and was generated by Computable Publishing's FEvIR (FHIR Evidence in Resources) Converter.
+
+---
+
+## Interpretation
+
+NCT01797120 (PrE0102) is a Phase 2 trial demonstrating that adding everolimus (mTOR
+inhibitor) to fulvestrant approximately doubles median PFS in postmenopausal women with
+AI-resistant HR+ metastatic breast cancer (10.3 vs. 5.1 months). The result is mechanistically
+consistent with the Phase 3 BOLERO-2 trial (everolimus + exemestane) and supports the
+hypothesis that PI3K/mTOR pathway activation is a key driver of endocrine resistance in
+this setting. The clinical benefit rate of 63.6% in the combination arm underscores meaningful
+disease control in a population with limited options after AI failure.